
COPYRIGHT DEPOSIT: 



1 



A TEXT-BOOK 

of 

PATHOLOGY 



BY 

ALFRED STENGEL, M. D., Sc. D. 

Professor of Medicine, University of Pennsylvania; Physician to the Pennsylvania 
and to the University Hospitals 

AND 

HERBERT FOX, M. D. 

Director of the Pepper Laboratory of Clinical Medicine, University of Pennsylvania; 
Pathologist to the Philadelphia Zoological Garden 



SIXTH EDITION, RESET 

WITH 468 TEXT ILLUSTRATIONS, MANY 
IN COLORS, AND 15 COLORED PLATES 



PHILADELPHIA AND LONDON 



W. B. SAUNDERS COMPANY 

1915 



Copyright, 1898, by W. B.' Saunders. Revised, reprinted, and recopyrighted March, 
1899. Reprinted August, 1899 ; November, 1899. Revised, reprinted, and recopy- 
righted October, 1900. Reprinted July, 1901 ; September, 1902. Revised, 
reprinted, and recopyrighted July, 1903. Reprinted March, 1905, 
Revised, reprinted, and recopyrighted September, .1906. Re- 
printed November, 1907, August, 1909, August, 1910, 
1 July, 1911, and June, 1912. Revised, entirely 

reset, reprinted, and recopyrighted 
August, 1915 

J . 

Copyright, 1915, by W. B. Saunders Company 



PRINTED IN AMERICA 



PRESS OF 
W, B. SAUNDERS COMPANY 
PHILADELPHIA 

©CI.A411230 
AUG 27 1915 



PREFACE TO THE SIXTH EDITION 



In the preparation of the present (the sixth) edition of the Text- 
book of Pathology I am fortunate in having the co-operation of 
Dr. Herbert Fox, whose active interest in general and comparative 
pathology and in clinical pathology peculiarly fit him for collabora- 
tion in a book designed especially for the needs of students and prac- 
titioners preparing for or engaged in the work of practical medicine. 
The book hereafter will appear under our joint authorship, each 
having contributed largely to the present edition. 

Extensive revision has been found necessary to bring the work 
fully to date. In the first portions, devoted to general pathology, 
the sections on Inflammation, Retrogressive Processes, Disorders of 
Nutrition and Metabolism, General Etiology, and Diseases due to 
Bacteria have been very largely recast or almost wholly rewritten. 
A new section on Transmissible Diseases has been added; the Terata 
have been incorporated with a brief synoptical chapter on Teratology; 
the Glands of Internal Secretion and their pathology have been made 
the subject of a separate chapter; and new sections on the pathology 
of the eye, ear, and skin, brief and general in scope, but, we hope, 
sufficient for a work of this character, have been added. It has 
seemed best to us to omit the chapter on Technic, which formed a 
part of previous editions, because the necessary brevity of such a 
chapter deprives it of practical usefulness. Special works on technic 
should be consulted by the student and laboratory worker. The 
chapters on Diseases of the Nervous System occupied a dispropor- 
tionately large part of previous editions and have, therefore, been 
curtailed. Numerous revisions have been made in other sections and 
chapters of special pathology where advances in knowledge have re- 
quired such alterations. Many new illustrations — upward of 100 in 
black and white or color — have been added, and by reason of the 
liberal policy of the publishers, to whom our thanks are due, the 
whole work has been reset and appears in a new and greatly improved 
form. 

Alfred Stengel. 

Philadelphia, Pa., August, 1915. 

7 



V 



CONTENTS 



PART I— GENERAL PATHOLOGY 



CHAPTER I page 

The Etiology of Disease 19 

Pathological Disposition, 20 — Traumatism, 24 — Physical Conditions, 25 
— Poisons, 29 — Vegetable and Animal Parasites, 37. 

CHAPTER II 

Disorders of Nutrition and Metabolism 39 

Food, 39 — Diminished Supply of Food, 39 — Increased Supply of Food, 40 



— Metabolism of Fat, 40 — Excessive Tissue Destruction, 40 — Acid Intoxi- 
cation, 42 — Disorders of Protein Metabolism, 44 — Disorders of Purin 
Metabolism, 45 — Gout, 46 — Diseases of Carbohydrate Metabolism, 47 — 
Diabetes Mellitus, 49— Fever, 53. 

CHAPTER III 

Disturbances of the Circulation of the Blood 56 

General Disturbances, 56 — Local Anemia, 58 — Local Hyperemia, 59 — 
Hemorrhage, 60 — Embolism, 64 — Infarction, 66 — Thrombosis, 67 — Edema, 
72. 

CHAPTER IV 

Retrogressive Processes 76 

Atrophy, 76 — So-called Infiltrations and Degenerations, 78 — Cloudy 
Swelling, 78 — Fatty Infiltration, 80 — Fatty Degeneration, 82 — Albuminoid 
Degenerations, 85 — Hyaline Degeneration, 85 — Mucoid Degeneration, 88 — 
Colloid Degeneration, 90 — Amyloid Infiltration, 91 — Glycogenic Infiltration, 
94 — Dropsical Infiltration, 95 — Calcification, 96 — Ossification, 98 — TJratic 
Infiltration, 98 — Pigmentation, 99 — Necrosis, 105 — Coagulation Necrosis, 
107 — Liquefaction Necrosis, 109 — Caseation, 110 — Fat Necrosis, 111 — 
Gangrene, 112 — General Pathology of Cellular Necrosis, 114 — Alterations 
in Cell Nuclei in Necrosis, 114 — Alterations in Form of Cells in Necrosis, 
114 — Altered Karyokinesis in Necrotic Cells, 115 — Postmortem Altera- 



tions, 115. 

CHAPTER V 

Inflammation and Regeneration 117 

Inflammation, 117 — Regeneration, 149 — Metaplasia, 155. 

CHAPTER VI 

Progressive Tissue Changes 157 

Hypertrophy, 157 — Tumors, 158. 



Connective Tissue Tumors, 169 — Fibroma, 169 — Myxoma, 173 — Lipoma, 
174 — Xanthoma, 175 — Chondroma, 176 — Osteoma, 179. 

9 



10 



CONTENTS 



PAGE 

Angiomata, 181 — Lymphangioma, 181 — Hemangioma, 182 — Lymph- 
adenoma, 184 — Sarcoma, 189 — Spindle-celled Sarcoma, 192 — Round-celled 
Sarcoma, 193 — Giant-celled Sarcoma, 195 — Melanosarcoma, 197 — Mixed 
Tumors, 198 — Mycosis Fungoides, 199 — Angiosarcoma, 200 — Cylindroma, 
202— Endothelioma, 203— Psammoma, 204. 

Tumors from Nerve Tissues, 204 — Glioma, 205 — Glioma Ganglionare, 
207 — Neuroma, 208 — Leiomyoma, 209 — Rhabdomyoma, 211. 

Epithelial Tumors, 212 — Papilloma, 212 — Adenoma, 215 — Carcinoma, 
219 — Epithelioma, 227 — Glandular Carcinoma, 229 — Special Forms of 
Cancer, 230— Cysts, 231— Epithelial Cysts, 232. 

CHAPTER VII 

Teratology 235 

Teratomata, 235— Dermoid Cyst, 236— Other Teratoid Tumors, 236— 
Syncytioma Malignum, 238 — Terata or Monsters, 239. 

CHAPTER VIII 

Bacteria, Their Nature and Action 241 

Classification, 241 — Morphology, 243 — Biology, 245 — Functions and 
Products of Bacteria, 247 — Products in Culture-medium, 250 — Local 
Effects of Bacteria, 251 — Effect of Toxic Products of Bacteria, 251 — Im- 
munity, 255. 

CHAPTER IX 

Diseases Due to Bacteria 273 

Diseases Due to Cocci, 273 — Suppurative Diseases, 273 — Gonorrhea, 278 
— Croupous Pneumonia, 280 — Other Forms of Pneumonia, 283. 

Diseases Due to Bacillary Forms, 285 — Diphtheria, 285 — Typhoid Fever, 
289 — Bacillus Coli Communis, 295 — Dysentery Bacillus, 297 — Influenza, 
298 — Bordet-Gengou Bacillus of Whooping-cough, 299 — Bubonic Plague, 
300— Soft Chancre, 302— Malta Fever, 303— Rhinoscleroma, 303— Gland- 
ers, 304— Tetanus, 306— Anthrax, 308— Malignant Edema, 311— Infectious 
Emphysema, 312 — Tuberculosis, 313 — Pseudotuberculosis, 324 — Fowl- 
tuberculosis, 325 — Leprosy, 326 — Bacterium Mucosum Capsulatum Group, 
329. 

Diseases Due to Spirilla, 330 — Cholera, 330 — Organisms Resembling the 
Cholera Vibrio, 333. 

Diseases Due to Spirochetes, 334 — Syphilis, 334 — Relapsing Fever, 339 
— Vincent's Angina, 340 — Frambesia or Yaws, 341. 

Diseases Due to Higher Bacteria, 341 — Actinomycosis, 341 — Mycetoma, 
346 — Thrush, 347 — Saccharomycosis or Blastomycosis, 348. 

Other Bacteria Not Causing Specific Infection, 349— The Hemorrhagic 
Diseases, 349 — Proteus Infection, 350. 

Infectious Diseases Whose Cause is Not Certainly Known. Filterable 
Viruses, 351— Yellow Fever, 351— Measles, 352— Scarlet Fever, 353— 
Mumps, 354— Variola and Vaccinia, 354— Varicella, 355— Typhus Fever, 
355— Rabies, 356— Rheumatism, 358— Beriberi, 359— Pellagra, 360— 
Dengue, 360— Poliomyelitis, 361— Foot-and-mouth Disease, 362— Tra- 
choma, 362 — Rocky Mountain Fever, 362 — Chlamydozoa, 363. 

CHAPTER X 

Animal Parasites and Diseases Caused by Them 364 

Protozoa, 364 — Rhizopoda, 364 — Entamoeba Histolytica, 364 — Enta- 
moeba Coli, 366 — Other Amebae, 366 — Mastigophora, 366 — Cercomonas 



CONTENTS 



11 



Hominis, 366— Cercomonas Coli Hominis, 367— Trichomonas Intestinalis, 
367— Trichomonas Vaginalis, 368— Other Forms of Trichomonas, 368— 
Lamblia Intestinalis, 368— Trypanosoma, 369— Hemosporidia, 372— 
Parasites of Malaria, 372— Coccidia, 377— Coccidium Cuniculi, 377— 
Sarcosporidia, 378— Infusoria, 379— Balantidium Coli, 379— Animal Para- 
sites and Molluscum Contagiosum, 379. 

Vermes, 380 — Trematodes, or Fluke-worms, 380 — Fasciola Hepatica, 380 
— Dicrocoelium Lanceatum, 381 — Opisthorchis Felineus, 382 — Opistorchis 
Sinensis, 382 — Schistosomum Haematobium, 382 — Schistosomum Japoni- 
cum, 383 — Paragonimus Westermanii, 383 — Other Fluke-worms, 384. 

Cestodes, or Tapeworms, 384 — Taenia Solium, 386 — Taenia Saginata, 388 
— Hymenolepis Nana, 389— Hymenolepis Diminuta, 389— Dipylidium 
Caninum, 390— Davainea Madagascariensis, 390— Taenia Echinococcus, 390 
— Dibothriocephalus Latus, 393— Dibothriocephalus Cordatus, 394— Both- 
riocephalic Mansoni, 394— Diplogonoporus Grandis, 394. 

Nematodes, or Round Worms, 395— Ascaris Lumbricoides, 395— Ascaris 
Canis, 395— Oxyuris Vermicularis, 396— Trichinella Spiralis, 396— Ankylos- 
toma Duodenale, 397— Necator Americanus, 399— Strongyloides Intestina- 
lis, 400— Trichocephalus Tricliiuris, 401— Filaria Medinensis, 401— Filaria 
Bancrofti, 402— Other Forms of Filariae, 404— Echinorhynchus Gigas, 404 
— Eustrongylus Gigas, 405— Strongylus Apri, 405— Strongylus Subtilis, 405 
— Annelides, 405— Arthropoda, 405— Linguatula Rhinaria, 406— Poroceph- 
alus Constrictus, 406 — Myiasis, 406. 

CHAPTER XI 

The Methods of Transmission of the Communicable Diseases 407 

Direct Infection, 408 — Indirect Transmission, 409. 



PART II— SPECIAL PATHOLOGY 



CHAPTER I 

Diseases of the Blood 412 

Anatomy, 412 — Blood Formation, 419 — Pathological Changes in the Red 
Corpuscles, 420 — Pathological Changes in the Leukocytes, 422 — Patholog- 
ical Changes in the Plasma, 423 — Plethora, 424 — Oligemia, 424 — Hydremia 
and Anhydremia, 425 — Lipemia, 425 — Melanemia, 426 — Hemocytolysis; 
Hemoglobinemia, 426 — Polycythemia, 427 — Leukocytosis, 428 — Leuko- 
penia, 430 — Anemia, 431 — The Secondary Anemias, 431 — The Primary 
Anemias, 433 — Chlorosis, 433 — Progressive Pernicious Anemia, 435 — 
Aplastic Anemia, 437 — Hemolytic Ictero-anemia, 438 — Leukemia, 438 — 
Hodgkin's Disease, 441— Pseudoleukemia Infantum, 441 — Foreign Bodies 
and Parasites, 442. 

CHAPTER II 

Diseases of the Lymphatic Tissues 443 

Spleen, 443 — Abnormal Development and Situation, 444 — Circulatory 
Disturbances, 444 — Inflammation, 445 — Atrophy and Degenerations, 448 — 
Leukemia and Hodgkin's Disease, 449 — Tumors and Parasites, 449 — 
Infectious Diseases, 450. 



12 



CONTENTS 



Lymphatic Glands, 450 — Atrophy, 452 — Hypertrophy, 452 — Status 
Lymphaticus, 452 — Degenerations, 453 — Inflammation, 454 — Infectious 
Diseases, 456 — Leukemia and Hodgkin's Disease, 459 — Tumors, 461. 

Bone-marrow, 462 — Degenerations, 463 — Atrophy, 464 — Hypertrophy, 
464 — Inflammation, 465 — Tumors, 466. 

CHAPTER III 

Diseases of the Circulatory System 467 

Heart, 467 — Congenital Diseases and Deformities, 468 — Circulatory 
Disturbances, 471 — Endocardium, 472 — Inflammation, 473 — Myocardium, 
481 — Degenerations, 481 — Inflammation, 486 — Hypoplasia and Atrophy, 
492 — Hypertrophy and Dilatation, 494 — Aneurysm, 496 — Wounds and 
Rupture of Heart, 497 — Infectious Diseases, 497 — New Growths and Para- 
sites, 497 — Pericardium, 498 — Circulatory Disturbances, 498 — Inflamma- 
tion, 498 — Infectious Diseases, 502— Tumors and Parasites, 502 — Pneumo- 
pericardium, 503. 

Arteries, 503 — Congenital Defects, 503 — Hypertrophy, 503 — Atrophy, 
504 — Degenerations, 504 — Inflammation, 505 — Infectious Diseases, 511 — 
Aneurysm, 511. 

Veins, 517 — Circulatory Disturbances, 517 — Degenerations, 518 — In- 
flammation, 518 — Dilatation, 519 — Tumors, 520 — Infectious Diseases, 520. 

Lymphatic Channels, 521 — Inflammation, 521 — Dilatation, 521 — Infec- 
tious Diseases, <522 — Tumors, 522 — Parasites, 523. 

Thoracic Duct, 523. 

CHAPTER IV 

Diseases of the Respiratory System 524 

Nasal Cavities, 524 — Congenital Abnormalities, 524 — Circulatory Dis- 
turbances, 524 — Inflammations, 525 — Infectious Diseases, 525 — Tumors, 

526 — Parasites and Foreign Bodies, 526. 

Larynx, 526 — Congenital Abnormalities, 526 — Circulatory Disturbances, 

527 — Inflammations, 527 — Infectious Diseases, 528 — Tumors, 529 — Para- 
sites and Foreign Bodies, 530. 

Trachea, 530 — Malformations, 530 — Circulatory Disturbances, 531 — 
Inflammations, 531 — Infectious Diseases, 531 — Tumors, 531. 

Bronchi, 531— Congenital Malformations, 532 — Circulatory Disturbances, 
532 — Inflammations, 532 — Stenosis and Obstruction, 534 — Dilatation, 535 
—Infectious Diseases, 536 — Tumors, 536 — Parasites and Foreign Bodies, 
537. 

Lungs, 537 — Congenital Defects, 538 — Circulatory Disturbances, 538— 
Hypertrophy and Atrophy, 543 — Emphysema, 543 — Atelectasis, 546— 
Inflammation or Pneumonia, 548 — Gangrene, 565 — Infectious Diseases, 566 
Syphilis, 578— Glanders, 579— Actinomycosis, 580 — Tumors, 580— Para- 
sites, 584. 

Pleura, 585 — Inflammation, 586 — Infectious Diseases, 591 — Tumors and 
Parasites, 592. 

CHAPTER V 

Diseases of the Gastro-intestinal Tract 594 

Mouth, 594 — Congenital Abnormalities, 594 — Circulatory Disturbances, 
594 — Inflammation, 594 — Atrophy and Degenerations, 598 — Infectious 
Diseases, 598— Tumors, 600. 
Teeth, 601. 



CONTENTS 



13 



Pharynx and Tonsils, 602 — Circulatory Disturbances, 602 — Inflamma- 
tions, 602 — Pressure Necrosis, 606 — Infectious Diseases, 606 — Tumors, 608. 
Salivary Glands, 608. 

Esophagus, 609 — Congenital Defects, 609 — Circulatory Disturbances, 
609 — Inflammations, 610 — Stenosis, 610 — Dilatation, 611 — Perforation and 
Rupture, 611 — Infectious Diseases, 612 — Tumors, 612. 

Stomach, 613 — Congenital Defects, 613 — Circulatory Disturbances, 613 
— Inflammation, 614 — Gastric Ulcer, 617 — Atrophy and Degenerations, 620 
— Alterations in Position and Size, 621— Infectious Diseases, 622 — Tumors, 
622. 

Intestines, 626 — Congenital and Acquired Abnormalities, 626 — Intestinal 
Obstruction, 629— Prolapse of Rectum, 630— Atrophy and Degenerations, 
631 — Circulatory Disturbances, 631 — Inflammations, 633 — Inflammations 
of Special Parts, 635— Infectious Diseases, 639— Tumors, 648— Parasites, 
651 — Intestinal Rupture and Foreign Bodies, 652. 

Liver, 653— Malformations and Changes of Position, 653— Circulatory 
Disturbances, 654 — Atrophy and Degenerations, 657 — Rupture of the 
Liver, 671 — Infectious Diseases, 671 — Tumors, 673 — Parasites, 677. 

Biliary Ducts and Gail-Bladder, 678— Inflammations, 678 — Stenosis and 
Dilatation, 680— Gall-stones; Cholelithiasis, 681— Tumors, 683— Jaundice, 
683. 

Pancreas, 685 — Congenital Abnormalities, 685 — Circulatory Disturb- 
ances, 685 — Atrophy and Degenerations, 685 — Inflammations, 687 — Infec- 
tious Diseases, 689 — Tumors, 689 — Pancreatic Duct, 690. 

Peritoneum, 691 — Congenital Abnormalities, 691 — Circulatory Disturb- 
ances, 691 — Inflammations, 693 — Infectious Diseases, 696 — Tumors, 698 — 
Parasites, 698. 

CHAPTER VI 

Diseases of the Ductless Glands 699 

Thyroid Gland, 699 — Congenital Defects, 699 — Disturbances of Circula- 
tion, 699 — Inflammations, 700 — Struma or Goiter, 700 — Infectious Diseases, 
705 — Tumors and Parasites, 705 — General Results of Thyroid Disease, 705. 

Suprarenal Bodies, 708 — Congenital Anomalies, 709 — Degenerations, 709 
— Infectious Diseases, 709 — Circulatory Disturbances, 710 — Inflammation, 
711— Tumors, 711. 
Thymus Gland, 711. 

Pituitary Body, or Hypophysis Cerebri, 712. 
Pineal Gland, or Epiphysis Cerebri, 715. 

CHAPTER VII 

Diseases of the Urinary Organs 717 

Kidneys, 717 — Congenital Anomalies, 717 — Changes of Position, 717 — 
Circulatory Disturbances, 718 — Inflammations, 720 — Nephritis, 720 — 
Acute Parenchymatous Nephritis; Bright's Disease, 722 — Acute Inter- 
stitial Nephritis, 724 — Chronic Nephritis, 726 — Chronic Parenchymatous 
Nephritis, 726 — Chronic Interstitial Nephritis, 729 — Atrophy and Hyper- 
trophy, 737 — Degenerations, 737 — Concretions in Uriniferous Tubules, 740 
— Infectious Diseases, 741 — Tumors, 741 — Parasites, 747. 

Pelvis of Kidney and Ureter, 748 — Congenital and Acquired Malforma- 
tions, 748 — Calculus, 749 — Inflammation, 749 — Infectious Diseases, 750 — 
Tumors, 751 — Parasites, 751. 



14 



CONTENTS 



PAGE 

Urinary Bladder, 752 — Malformations, 752 — Changes of Position, 752 — 
Rupture, 753 — Circulatory Disturbances, 753 — Inflammation, 753 — In- 
fectious Diseases, 755 — Calculi and Foreign Bodies, 755 — Tumors, 757 — 
Abnormal Conditions of Urine, 758 — Chemical Changes and Sediments, 764. 

Urethra, 766 — Inflammations, 767 — Injuries, 770 — Infectious Diseases, 
770— Tumors, 770. 

CHAPTER VIII 

Diseases of the Reproductive Organs 771 

Uterus, 771 — Congenital Abnormalities, 771 — Alterations of Position, 
772 — Stenosis, Dilatation, and Rupture, 775 — Circulatory Disturbances, 
775 — Inflammations, 777 — Infectious Diseases, 780 — Atrophy and Degen- 
eration, 783 — Hypertrophy and Hyperplasia, 783— Tumors, 784 — Parasites, 
790. 

Ovaries, 790— Congenital Abnormalities, 790 — Changes in Position, 790 
— Circulatory Disturbances, 791— Inflammation, 791— Infectious Diseases, 
792— Tumors, 792— Cysts of Parovarium, 796— Cysts of Kobelt, 797. 

Fallopian Tubes, 797— Congenital Abnormalities, 797— Changes of Posi- 
tion, 797 — Stenosis, 798— Dilatation, 798— Circulatory Disturbances, 798— 
Inflammations, 799— Infectious Diseases, 801— Parametrium, 803— Extra- 
uterine Pregnancy, 803. 

Vagina, 805— Prolapse of Walls, 805— Stenosis, 805 — Wounds and . 
Fistula, 805 — Circulatory Disturbances, 806 — Inflammations, 806 — Infec- 
tious Diseases, 807 — Tumors, 807. 

Vulva, 807 — Wounds, 808 — Circulatory Disturbances, 808 — Inflamma- 
tion, 808 — Infectious Diseases, 809 — Tumors, 809. 

Decidua, Placenta, and Fetal Membranes, 810 — Abnormalities of Devel- 
opment, 810 — Circulatory Disturbances, 811 — Inflammation, 811 — Infec- 
tious Diseases, 812 — Hyperplasia, 812. 

Penis and Scrotum, 814 — Congenital Abnormalities, 814 — Inflammation, 
814 — Infectious Diseases, 815 — Tumors, 815 — Injuries, 816. 

Testicles, 816 — Anatomical and Physiological- Considerations, 816 — 
Congenital Abnormalities, 816 — Atrophy and Hypertrophy, 817 — Degenera- 
tions, 817 — Circulatory Disturbances, 818 — Inflammation, 818 — Infec- 
tious Diseases, 821 — Tumors, 822 — Parasites, 824. 

Prostate Gland, 824 — Inflammation, 824 — Atrophy and Degeneration, 
824 — Concretions, 825 — Infectious Diseases, 825 — Hypertrophy and 
Tumors, 825. 

Cowper's Glands, 828. 

Seminal Vesicles, 828. 

Mammary Glands, 829 — Congenital Abnormalities, 829 — Circulatory 
Disturbances, 829 — Inflammations, 829 — Atrophy and Hypertrophy, 830 — 
Degenerations, 831 — Infectious Diseases, 831 — Tumors, 831. 

CHAPTER IX 

Diseases of the Bones 836 

Disorders of Development, 836 — Rickets, 837 — Regeneration, 839 — 
Circulatory Disturbances, 841 — Inflammations, 842 — Degenerative Condi- 
tions, 846 — Hypoplasia and Atrophy, 847 — Infectious Diseases, 849 — 
Tumors, 853. 

CHAPTER X 

Diseases of the Joints 855 

Distortions, 855 — Circulatory Disturbances, 856 — Inflammations, 856 — 
Infectious Diseases, 860 — Tumors, 862 — Tendon-sheaths and Bursae, 862. 



CONTENTS 



15 



CHAPTER XI 

Diseases of the Voluntary Muscles 863 

Hypertrophy, 863 — Circulatory Disturbances, 863 — Inflammations, 864 
— Atrophy and Degenerations, 866 — Infectious Diseases, 869 — Tumors and 
Parasites 869. 

CHAPTER XII 

Diseases of the Brain and Its Membranes 870 

Dura Mater, 870 — Circulatory Disturbances, 870 — Infectious Diseases, 
872— Tumors, 872— Cysts, 873. 

Pia-arachnoid, 873 — Circulatory Disturbances, 874 — Inflammation, 874 
—Infectious Diseases, 878— Tumors, 880. 

Brain, 882 — Development and Anatomy, 882 — Postmortem Degenera- 
tive Conditions, 886 — Congenital Abnormalities, 887 — General Pathological 
Anatomy of Nervous System, 891 — Blood-vessels, 900 — Circulatory Dis- 
turbances, 902 — Inflammation, 910 — Injuries to Central Nervous System, 
917— Infectious Diseases, 918— Tumors, 919— Choroid Plexus, 922. 

CHAPTER XIII 

Diseases of Spinal Cord and Its Membranes 928 

Dura Mater, 928. 

Pia-arachnoid, 929 — Circulatory Disturbances, 929 — Degenerations, 929 
— Inflammations, 930 — Infectious Diseases, 930. 

Cord, 931 — Anatomy, 931 — Congenital Abnormalities, 933 — Hydromy- 
elia and Syringomyelia, 934 — Circulatory Disturbances, 936 — Inflamma- 
tion, 938 — Primary Degenerations, 943 — Secondary Degenerations, 953 — 
Tumors, 957. 

CHAPTER XIV 

Diseases of the Peripheral Nervous System 958 

Ganglia of Cranial and Spinal Nerves, 958. 

Nerves, 958 — Circulatory Disturbances, 958 — Regeneration after Injury, 
959 — Inflammations, 960 — Infectious Diseases, 962 — Tumors, 963. 

CHAPTER XV 

The Eye. 964 

Anatomy, 964 — Congenital Abnormalities, 965 — Conjunctiva, 965 — ■ 
Lachrymal Organs, 970 — Cornea, 970 — Sclera, 972 — Crystalline Lens, 973 — 
Vitreous Humor, 974— Iris, 974— Ciliary Body, 976— Choroid, 977— Retina, 
978— Sympathetic Ophthalmitis, 980— Glaucoma, 980— Optic Nerve, 981— 
Orbit, 983— Lids, 983. 

CHAPTER XVI 

The Ear : 984 

Anatomy, 984 — Congenital Defects, 985 — External Ear, 985 — Tympanic 
Membrane, 986— Tumors of External Ear, 986— Middle Ear, 987— Eu- 
stachian Tube, 989— Internal Ear, 989. 

CHAPTER XVII 

The Skin 990 

Anatomy, 990 — Congenital Abnormalities, 991 — Atrophy, Hypertrophy, 
and Degenerations, 991 — Variations in Pigmentations, 993 — Circulatory 
Disturbances, 993 — Inflammation (Dermatitis), 994 — Specific Inflamma- 
tions, 1002— Tumors, 1005. 

Structures Within the Skin, 1006— Sebaceous Glands, 1006— Sweat- 
glands, 1007— Hair, 1008— Nails, 1008. 



Index :• 1009 



I 



A TEXT-BOOK OF PATHOLOGY 

PART I 
GENERAL PATHOLOGY 

Pathology is the science that deals with disease in all its aspects. 
It includes the study of the causes, the manifestations, and the results 
of disease. 

Three important subdivisions of the study of pathology are recog- 
nized, viz., etiology, or the study of the causes of disease; morbid or 
pathological anatomy, the study of the gross and microscopical structural 
changes in disease; and morbid or pathological physiology, the study of 
disturbances of function. In the latter group is included pathological 
chemistry, as morbid chemical action and its results are the outcome 
of disturbed function. 

Pathology may be divided into general and special pathology. 
The former treats of causes of disease and pathological processes irre- 
spective of any individual part; the latter deals with the causes or 
processes in individual diseases, organs, or parts. 

Disease itself is not a separate entity, but may be defined as ab- 
normality in structure, in function, or in both combined. It is doubt- 
ful whether alteration of function can occur without some alteration 
in structure, but it frequently happens that functional disturbances 
are present though no structural alterations are discoverable even by 
the most precise methods of investigation. 

It is obvious from the foregoing that it is impossible to define sharply 
either disease or health. Health, or fully harmonious action of all 
physical and physiological units, is subject to the same laws of mode and 
mean as any other group of varying but comparable units, and as the 
examples or phenomena digress from the mean, they approach the 
abnormal or the unnatural. This will suggest the merging of the healthy 
into the diseased state. Assuming further that health is controlled by 
a harmonious and uniform set of impulses, the interruption of one of 
them or the introduction of a foreign stimulus will unbalance the cycle, 
or the natural impulses may be destroyed by the foreign intrusion. 
Many slight abnormalities of stimulation or minor intrusions are quickly 
removed and the general physiology rights itself promptly. If, how- 
2 17 



is 



A TEXT-BOOK OF PATHOLOGY 



ever, the interruption or intrusion affect an important structure, an 
organ like the liver or lung, the cycle of physiology of the remaining 
parts must be constructed upon a new temporary plan in a compensa- 
tory manner. The various organs or systems have different values in 
throwing compensatory work upon others. For example, the failing 
lung throws work upon the kidneys, skin, and intestines, and the failing 
heart strains the lungs and kidneys. Organs in pairs complement 
each other or one may attempt to assume the duties of both. The loss 
of the liver or kidneys is incompatible with life, while a large part of these 
organs or even of the brain may be destroyed without cessation of life. 

The gross alteration in diseased organs is fundamentally the effect 
of pathological changes in constituent cells, as Virchow's philosophy 
has taught us. The severity of an abnormality stands in direct re- 
lation to the number of cells affected, the degree of change, and the 
importance of the cells. The more highly specialized a cell, the less 
able it is to regenerate its kind, and, therefore, the more lasting is the 
effect of its destruction. The cells of the brain and the germ cells do 
not reproduce. 

While disease is still viewed as a process which begins anatomically, 
it is obvious from the above that all diseased states are probably pre- 
ceded or at least always accompanied by chemical and physiological dis- 
turbances. This part of the subject will be taken up in particular in 
the next chapter. The cause of these anatomical and chemical changes 
are factors either within or without the body. The specific diseases 
are usually indicated by an equally specific set of anatomical and 
chemical changes from the normal. 

The symytoms of disease are the expressions of abnormal functional 
activity, and are, therefore, properly discussed under the head of 
Pathological Physiology; but they are so important from a practical 
standpoint, and form so extensive a subject of investigation, that they 
are usually considered apart from pathology, in special treatises dealing 
with diagnosis and the practice of medicine. 



CHAPTER I 



THE ETIOLOGY OF DISEASE 

The study of the causation of disease embraces and must account 
for the predisposing factors and the determining causes. The former 
prepare the system and make it susceptible to the latter, or immediate 
and specific causes of disease. 

The predisposing factors may increase the receptivity of the body for 
more than one kind of disease agent. The term "predisposition" is 
at times used for a hereditary or acquired tendency toward certain 
diseased states. Thus, one might exemplify hereditary predisposition 
by the lowered resistance to tuberculosis of the young of tuberculous 
parents. Another phase of this hereditary influence is shown in the 
tendency for cells to exhibit an abnormal metabolism because of a 
family or hereditary tendency, and leading to abnormal states of 
health (Baumgarten's anlage). (See Heredity.) Acquired predispo- 
sition is due to vices of living, previous disease, or to a summation of 
several predisposing factors leading in one direction. This has been 
termed "disposition" by some writers. 

Predisposing Factors. — The normal system is able to cope with 
the determining causes of disease to a certain point by its general 
vitality and regulative functions. Thus, heat and cold may prove 
harmless if not too intense or prolonged. In the case of exposure to 
heat, the superficial capillaries become dilated, sweating increases, and 
there is increased heat dissipation from the surface at the same time 
that increased respiratory function occasions evaporation and loss of 
heat through the lungs. In the case of exposure to cold, increased muscu- 
lar exercise leads to greater heat production, while contraction of the 
superficial blood-vessels restricts the elimination of heat. When, 
however, a certain point of intensity is reached in the case of heat, cold, 
or other causes of disease, the normal organism is unable to oppose 
sufficient resistance, and disease or injury results. Chemical relations in 
body cells and fluids, such as equilibrum of colloids in solid and liquid 
condition or enzyme power, may be destroyed by prolonged exposure 
to heat and cold, and the former may also destroy red blood-cells. 
The degree of resistance differs in different individuals, in different 
races, or people living under varying climatic conditions, etc. In 
some the degree of resistance may be so great that certain diseases are 
never contracted. The term immunity (q. v.) is applied to this state. 

Certain predisposing factors may now be taken up in order. 

1. Age. — This plays a large part in the vulnerability of an individual. 
The exanthemata are much more common in childhood, while car- 
cinoma is commonest in adult life. The rate of repair is also greater in 

19 



20 



A TEXT-BOOK OF PATHOLOGY 



youth. Tuberculosis assumes somewhat different forms when develop- 
ing in childhood, adolescence, or adult life. There is a decided varia- 
tion in the amount of protective antibody in the blood at different ages. 

2. Sex. — The influence of sex is not great aside from disease of the 
sexual organs. Man is subject to more traumatisms and diseases due to 
the wider social life he leads. He suffers more often from cancer, aside 
from genitalia, than the female. There are more cases of gout, diabetes, 
and organic nervous disease in men. Women are more often attacked 
by functional nervous diseases and affections of the thyroid gland. 

3. Race. — Certain peoples are prone to or immune against certain 
diseases. Negroes are resistant to malaria and endure yellow fever 
well. Aside from the unsanitary conditions in which many live, they 
have a low resistance to tuberculosis. The effect of zoological order is 
more pronounced than race differences. The dog is resistant to tuber- 
culosis; the chicken, to tetanus. This has hampered experimental work 
upon infectious diseases, because it is often difficult to fulfil Koch's pos- 
tulates (q. v.). 

4. Nutrition. — Failure to obtain wholesome pure food will, of course, 
reduce resistance. The presence of putrefaction or disease-producing 
agents will cause disease. Prolonged hunger reduces general resistance. 
Habits of any sort that tend to disturb digestion reduce resistance. 
The maintenance of what is apparently the amount of fat normal 
to the individual is helpful to resistance. The relation of bodily activity 
and stored-up reserve has an influence upon later demands of exertion. 

5. Idiosyncrasy is the peculiar susceptibility of individuals to cer- 
tain poisons or infections and sometimes even to ordinary foods. This 
should not be confused with diathesis or predisposition (q. v.). 

The presence of one infection may favor the reception of another. 

6. Conditions of life. Habitation in places infested with disease-trans- 
mitting insects materially influences morbidity. Unsanitary dwellings 
directly affect health. Occupation: Workers in paint suffer from lead- 
poisoning; handlers of hides contract anthrax; miners get anthracosis of 
the lungs. Prolonged mental anxiety has some depressing effect upon 
resistance. 

7. Injury. 

8. Heat and cold. 

9. Physical forces, like electricity and .T-ray, and atmospheric 
pressure. 

10. Poisons of all kinds. 

Items 1 to 5 may be called intrinsic or internal, while 6 to 10 are 
extrinsic or external. 

PATHOLOGICAL DISPOSITION 

Under this heading come those instances in which physical or 
physiological departures from the type or from the standard are expressed 
in the unusual susceptibility of the whole or a part. Idiosyncrasies 
might be classed here. This pathological disposition refers chiefly to 
those conditions in which slow healing of skin wounds or the lack of 



THE ETIOLOGY OF DISEASE 



21 



sweat and sebaceous secretions render the skin more susceptible to 
spreading infections. We might also include here the sensitive state of 
some individuals to certain organic proteins which makes them subject 
to intoxications with these compounds, not toxic to other persons. (See 
Immunity.) 

There is a related pathological disposition at seats of chronic in- 
flammation, chronic irritation, or chronic injury, as it has lately been 
called. Here malignant change may occur. 

Whether this pathological disposition is hereditary or acquired is 
difficult to say, as it is equally impossible to decide whether it is due to 
absence of immunity reactions. 

Occasionally organ or system disposition is mentioned, by which is 
meant a peculiar visceral distribution of lesions, which may be anatom- 
ical or physiological. It covers such instances as the frequency of 
infarction of the spleen and lung, and the involvement of the spleen in 
liver disease. 

Heredity or inheritance is a factor of importance in the etiology of 
disease. In some cases the disease itself is transmitted to the offspring, 
but more frequently the predisposition only. A distinction must be 
made between weakness of a child at birth (congenital weakness) and a 
definitely inherited weakness. Thus, an alcoholic mother or one sub- 
jected to hardships during pregnancy may give birth to a child which 
is feeble and lacking in resistance to disease. This feebleness is congen- 
ital, but not inherited. The same statement applies to diseases such as 
tuberculosis and syphilis, which may be acquired from the mother by 
the fetus in utero, but are not inherited. If the father is the original 
source of infection, he first infects the mother, from whom the child 
then acquires the disease. One cannot in these cases properly use the 
term "hereditary." 

Heredity, strictly speaking, applies only to the transmission of 
parental or ancestral characteristics to the offspring through the paren- 
tal germ-plasm. We may distinguish between racial, familial, and 
direct inheritance. The term direct inheritance indicates transmission 
from parent to offspring. The term indirect is sometimes used to 
indicate transmission of characters latent in one generation to subse- 
quent ones. Atavism is a more frequent designation of this derivation 
of characteristics from ancestors after they had been latent in one or 
more generations. In a broader sense the term "atavism" has also been 
applied to reversion to racial characteristics that had been dormant 
through many generations. Collateral inheritance is a term used in cases 
in which an individual manifests characters present in uncles, aunts, 
or other collaterals, but not in his parents or immediate ancestors. 
The laws of heredity explain this occurrence. 

In some cases there is crossed transmission. A peculiar form of 
heredity is seen in hemophilia and some other diseases, which are trans- 
mitted through the female members of a family, who generally remain 
unaffected, to the male offspring. Hereditary traits sometimes pre- 
dispose to a number of allied affections. This is particularly striking 



22 



A TEXT-BOOK OF PATHOLOGY 



in the case of the neuropathic heredity, in which various forms of 
nervous disease may appear alternately or irregularly in members of an 
affected family. 

Rossle says normal and pathological characters, but not diseases, are 
inherited. The ovum is not infected with the cause of syphilis, but the 
fetus is infected with the germ cells or through the placenta. The 
influence of maternal conditions is naturally the greater. Abnormalities 
in offspring of consanguineous parents are now explained as a summa- 
tion of the natural tendencies of both parents. 

Hereditary Congenital Pathological Conditions. — Such conditions as 
hemophilia and color-blindness, familial nervous disorders, joint mal- 
formations, and skin anomalies are placed in this group. 

Pathological Conditions of Later Life Depending Upon Heredity. — 
This heading refers to the related subjects of predisposition and diathetic 
reversion or inheritance. Such diseases as gout, diabetes, and insanity 
are covered. Here one may place the undeveloped physique and con- 
stitutional lack of resistance to tuberculosis in the children of affected 
parents. 

A number of theories have been constructed to explain the mechan- 
ism of heredity. Darwin, in his hypothesis of pangenesis, suggested that 
minute particles are given off from all of the cells of the body; these are 
collected in the reproductive cells, which, in consequence, represent all 
of the bodily characteristics, hereditary and acquired. Weismann 
denies the transmissibility of acquired characteristics, and holds that 
in the process of reproduction a certain amount of "germ-plasm" passes 
from the parent cell into the offspring, where it remains, and is in turn 
passed on to succeeding generations, thus perpetuating ancestral char- 
acteristics. 

Another theory of heredity is called epigenesis, or that process 
through which an ovum goes in its maturation process when it develops 
under its appropriate biological environment. This theory does not 
accept the statement that in the ovum there is a preformed molecule 
that will eventually develop into a particular part, as is the case with 
the two previous theories. It assumes that the development of the indi- 
vidual occurs in harmony with that of the race. 

However, it has been shown that with the earliest stages of a de- 
veloping ovum certain differentiations occur which apparently stand as 
forerunners of certain bodily parts, and the development depends upon 
the preserved integrity of these primary divisions of the ovum. It has 
also been shown that an embryo when dividing shows distinct polarity. 
These facts militated against the epigenetic theory and gave rise to the 
mosaic theory, which assumes the control of bodily parts by definite 
molecules or blastula segments. 

It must not be forgotten in the study of heredity that, while the 
atomical changes are measures of evolution and heredity, the chemistry 
of the biological mass must be similarly affected. If, as has been 
maintained by some authors, the disproportion between the surface 
tension in nucleus and protoplasm combined with alterations in the 



THE ETIOLOGY OF DISEASE 



23 



chemical consituents as a result of this, be the cause of cell growth, then 
any disturbance of the cell tension or chemistry will be felt by new 
cells the product of the division. If the parent cell has established 
for itself a definite chemical cycle its progeny will continue this cycle. 
This is another application of Baumgarten's anlage, and shows the close 
association of heredity and predisposition. 

The theories and experiments upon heredity have given rise to 
certain generalizations and laws which are now explained. 

Racial inheritance expresses itself in functional or anatomical varia- 
tion. Races are peculiar in resistance to parasitic diseases and in the 
maintenance of certain physical characters. 

Familial inheritance is similar in principle to the former, and is well 
illustrated in hemophilia (q. v.). 

Blended and Particulate Inheritance. — The former means a har- 
monious admixture of characters of the parent, while the latter means 
the domination of some particular character. Mendel's law : The 
observations of Gregor Mendel upon self-fertilizing plants showed the 
transmission of character to follow a very definite law. When two or- 
ganisms, one so-called dominant, the other recessive, reproduce, the off- 
spring contains a mixture of the two, although dominant characters 
may show more clearly. The second generation shows one pure dom- 
inant, two admixtures of dominant and recessive, and one recessive. 
Self-fertilization will produce always dominant from dominant and 
recessive from recessive. Offspring of admixtures will produce, as in 
the second generation, a dominant which will continue a dominant, a 
recessive following this type in its progeny, and mixtures of dominant 
and recessive and recessive and dominant. These last two will then 
follow the same course by producing two pure and two mixed prog- 
enies. This law has been worked out with many plants and some 
small animals. It has not been directly applied to man, but it is obvious 
that the domination of characters must have influence upon offspring. 
Galton's law claims that the parents each supply a quarter of the 
influence to the offspring; the four grandparents, each a sixteenth, 
and so backward to the completion of the unit. 

For the mosaic inheritance and atavism see above. 

Reversionary inheritance is atavistic reversion to a lower condition or 
incomplete type. 

Diathetic inheritance is a transmitted tendency in a particular 
direction. (See Pathological Disposition and Predisposition.) 

Cumulative inheritance is a summation or exaggeration of charac- 
ters from both parents. 

Mutation is the assumption of character not peculiar to the given 
species. 

Determining Causes. — Among the immediate or determining causes 
of disease are those which originate outside the body and those which 
are generated within the body. Among the former are included trau- 
matism, heat, cold, and other physical agents, poisons, and living organ- 
isms, including bacteria and various animal parasites. The causes of 



24 



A TEXT-BOOK OF PATHOLOGY 



disease originating within the body itself are less definitely known, but 
it has been found in chemical studies that various products of normal 
metabolism when accumulated in abnormal quantity, or products of 
disturbed metabolism, may occasion local or widespread disease of 
various sorts. This self-poisoning is designated auto-intoxication. 

The term "auto-intoxication" is frequently applied to poisoning by 
products of intestinal putrefaction. This application of the term is not, 
strictly speaking, correct. The same poisons might have been produced 
by putrefaction of food outside the body, when the use of the name auto- 
intoxication would be manifestly absurd. If poisons are produced by 
imperfect digestion, and these affect the organism, the condition could 
properly be termed auto-intoxication. 

TRAUMATISM 

Traumatism, or mechanical injury, may be of various sorts, gradual 
or sudden, small or large; and the effects are dependent upon the form 
and severity of the injury. Pressure brought to bear upon a part leads 
to disturbances of the circulation and more or less direct injury of the 
cellular elements. When the pressure is gradual, true atrophy of the 
part may occur, as in the case of the atrophic liver resulting from 
lacing. When the pressure is greater and the circulation is completely 
arrested, more destructive change may result, such as necrosis or gan- 
grene. This is seen in the necrotic atrophy of bone resulting from the 
pressure of aneurysms, or the gangrene of extremities resulting from 
ligation. Wounds. — Frequently, inflammatory reaction occurs in the 
surrounding tissues when traumatic injuries have been sustained. 
This is illustrated in all forms of wounds, and it is through the inflam- 
mation and subsequent regeneration of tissue that the areas of destruc- 
tion are restored. In cases of injury by fine particles, as in powder- 
marks of the skin, or the surface injuries sustained by miners and metal- 
workers, or in individuals inhaling sharp particles like coal-dust, marble- 
dust, or steel-filings, small injuries of the tissues result. The foreign 
bodies may be subsequently discharged, leaving a focus of inflamma- 
tion, or the inflammation may surround the particle embedded in the 
tissue, and encapsulation by fibrous-tissue formation may occur. 
Large injuries in which the tissues are contused or broken may lead to 
extensive inflammation, in part the result of the direct injury to the 
tissues and in part the result of injury of the blood-vessels. 

An injured surface presents a locus minoris resistentice which offers 
an entrance to organisms already in the locality or to those that might 
be actually driven into the tissue or blood-stream by the damaging 
force. 

Gross traumatism of the body as a whole, as in falls, crushing 
injuries, etc., causes various disturbances according to the part mainly 
involved. Rupture of the viscera, as the lungs, heart, liver, spleen, 
stomach, or intestines, may occur. When the head is violently struck, 
unconsciousness is common as a consequence of either disseminated 
punctiform hemorrhages, large focal hemorrhages, or obscure and 



THE ETIOLOGY OF DISEASE 



25 



possibly only functional disturbances. Commotio cerebri, the condition 
occurring in such cases, may be fugacious or may lead to permanent 
disorder dependent upon organic changes in the brain. Spinal symp- 
toms, met with after railway injuries and like accidents, may be due to 
hemorrhage and secondary morbid processes in the cord, or may be due 
to the uncertain pathological conditions constituting hysteria. 

The relation of a single trauma to tumors is not entirely clear. It 
seems that a new growth has been observed at a point where an in- 
jury has been sustained. Repeated minor traumata or continued irri- 
tation seem to precede some epithelial growths. The most notable 
example is the epithelioma of the lip of clay-pipe smokers. The injury 
in these cases can hardly be a determining cause. The occurrence of a 
tumor at a site of injury is not inconsistent with any of the principal 
theories of cancer origin. 

Epithelial cysts may arise at points of injury by the displacement of 
epithelial cells to a position below the surface. These are not true neo- 
plasms. 

PHYSICAL CONDITIONS 

Heat. — High temperatures produce local or general results ac- 
cording to the mode of application and degree of heat. 

Local excess of heat produces various lesions. Moderate excess leads 
to relaxation of the walls of the blood-vessels; with increasing grades of 
temperature there is, in addition, necrotic change in the cells of the part, 
and exudation of serum causes vesicle formation. Still higher grades 
of temperature produce immediate destruction, perhaps with charring, 
of large or small areas, while the surrounding tissues suffer from reactive 
inflammation and hyperemia. Extensive burns involving one-third 
or more of the surface of the body frequently cause death. In these 
cases it is likely that poisonous products are formed, either directly 
through tissue and blood destruction, or indirectly through disturb- 
ances of the functions of the skin or internal organs. The immediate 
manner of death is often in the form of shock ; when the termina- 
tion is delayed, various vascular, hemic, and tissue disturbances may 
occur. Intravascular coagulation is not unusual, and is not improbably 
the result of the liberation into the blood of tissue elements set free in 
the areas of local destruction, or to substances produced by direct 
destruction of the blood. The same substances may account for the 
existence of fever (ferment intoxication). The intravascular coagula- 
tion caused in this or other ways may induce venous stasis and localized 
hemorrhages. Focal necrosis or degeneration of the tissues of various 
organs, such as the liver, kidneys, or the mucous and serous membranes, 
may be due to thrombotic occlusion of vessels, or to the influence of cir- 
culating poisons without thrombosis, or to both. It seems probable 
that the cause of all these physical changes is a necrotizing toxin arising 
in the burned skin. (Some manifestations of this condition resemble 
anaphylaxis.) Marked changes are found in the lymphatic glands as 
well as in the Malpighian bodies of the spleen and in the bone-marrow. 
These changes present themselves as areas of leukocytic degeneration 



26 



A TEXT-BOOK OF PATHOLOGY 



containing actively phagocytic endothelial cells and surrounded by a 
zone of lymphocytic invasion. The lesions are not unlike those pro- 
duced by abrin, ricin, and bacterial toxins. Duodenal ulcer is often 
referred to as an occasional result of extensive burns. The blood itself 
may present evidence of disease in the form of degenerations of the 
corpuscles, in the reduction of their number, and of the amount of 
coloring-matter; while regenerative changes frequently present them- 
selves some time later (nucleated red corpuscles). Changes in the urine 
may occur in cases of extensive burns, in consequence of the tissue 
destruction (hemoglobinuria, albumosuria). 

Exposure to general high temperature varies in its effects according 
to the manner of exposure (dry air, steam, etc.). An animal exposed to 
a constant temperature somewhat above the usual surrounding tem- 
perature presents a slight increase of its body heat, which is compen- 
sated for by increase in the respirations and pulse-rate. Much higher 
temperatures may cause death by coagulation of the tissue proteins, 
notably in the muscular structure of the heart or the respiratory muscles. 
Before this extreme is reached, however, it may be found that the con- 
sumption of the tissues of the body is greatly in excess, though the res- 
piratory quotient is altered in favor of the amount of oxygen consumed. 
Continuous exposure to excessive heat frequently causes peculiar dis- 
turbances in man, known as heat-stroke, sunstroke or insolation and 
heat exhaustion. In these conditions hyperemia and edema, or even 
inflammation of the meninges, may occur. These lesions are some- 
times supposed to be the result of the direct effect of the heat; but there 
is reason to believe that they may be occasioned by poisonous substances 
produced within the body by disturbed metabolism, as a result of the 
heat. One evidence of the effect on the blood of continued elevation 
of temperature is the appearance in the red blood-corpuscles of baso- 
philic granules — granular degeneration of Grawitz. (See chapter on 
Blood.) Exposure to high temperatures for long periods, such as 
steamship stokers are subjected to, produces cramps in the muscles, 
chiefly of the extremities. The excitability of the muscles is greatly 
increased. 

The autopsy upon a death from heat-stroke shows an early rigor 
mortis and decomposition, general passive congestion due to weak heart 
action, a fluid condition of the blood, and sometimes hemorrhages into 
the medulla. 

A portion of the body, as an arm or a leg, may be exposed for a 
limited time to excessive temperatures (300° to 400° F.) in dry air 
without injury. The general temperature is slightly elevated, but 
metabolism is practically unaffected. 

The effects of general or local heat are much increased when the 
organism as a whole or in the part involved is below par. A paralyzed 
limb is burned or scalded at comparatively low temperatures. 

Cold. — Exposure to extreme degrees of cold may cause results 
quite similar to those produced by heat. Exposure of the skin to lique- 
fied air, solidified mercury, or other substances at excessively low 



THE ETIOLOGY OF DISEASE 



27 



temperatures produces vesiculation and necrosis of the tissues like those 
produced in burns. 

Exposure of the body to greatly reduced but bearable temperatures 
of the surrounding atmosphere causes vascular disturbances followed 
by necrosis of the tissues and inflammatory changes. The parts so 
affected are the extremities or projections of the body, like the toes 
and fingers, nose and ears. The primary result of cold is vascular 
constriction and local anemia. These serve the purpose of preserving 
the body heat by preventing heat radiation; later the blood-vessels are 
paralyzed and extreme hyperemia results. Then cellular exudation and 
necrosis may occur. These changes are well seen in the condition 
termed chilblain. In prolonged exposure to cold there are a gradual 
reduction in the activity of the various organs and a gradual obtunding 
of the sensibility until the patient becomes comatose. The retention 
of excrementitious products of metabolism, or the formation of products 
of abnormal metabolism, may be important in causing this condition. 
There is a reduction of hemoglobin and red cells, increase of C0 2 ex- 
cretion, and disappearance of glycogen. Autopsy shows edema of lungs, 
with or without congestion, and transudates into serous cavities. 

Exposure to cold plays an important part as a clinical cause of dis- 
ease. Various forms of pharyngitis and coryza or bronchitis so fre- 
quently follow such exposure that the term "cold" is generally used. 
Other conditions, like rheumatism, pleurisy, pneumonia, and the like, 
bear a similar relation. It is now recognized that in most of these 
cases cold is merely a predisposing cause, the immediate cause being 
in many, if not all, cases specific micro-organisms. The mode of action 
of the exposure is uncertain ; probably it causes a reduction in the resist- 
ing powers of the organism and thus favors the activity of bacteria. 
The hyperemia " following exposure to cold is associated with lowered 
alkalinity of the blood, thus favoring bacterial increase. The phago- 
cytic action of leukocytes is reduced by exposure to cold, and it is 
said that complement and antibody do not combine so readily with 
antigen. This is true in vitro. 

Increased Atmospheric Pressure. — Exposure to extreme pressure 
of several atmospheres may occur among deep-sea divers or in men 
working in caissons used in bridge building. But little disturbance may 
be caused at first or for a long time; but on return of the workmen to 
the usual atmospheric conditions symptoms make their appearance 
(caisson disease). Among these symptoms are bleeding from the nasal 
or other mucous membranes, great depression, delirium, and paralytic 
conditions. Congestion, degenerations, and vacuolations in the spinal 
cord have been discovered in some cases. 

The cause of the lesions is a hypertension of nitrogen within tissues. 
Tissues hold much more nitrogen than the blood, so that this gas is held 
in them because the blood becomes saturated each time it passes through 
the lungs. When the person returns to normal atmospheric pressure 
the tissues give up to the blood their retained gas. The blood and 
lungs can excrete but slowly, so that bubbles of nitrogen under release 



28 



A TEXT-BOOK OP PATHOLOGY 



of pressure appear in tissues and vessels. These bubbles are the cause 
of hemorrhages, fissures, and gas embolism. 

Decreased Atmospheric Pressure. — Effects of decreased press- 
ure are seen in inhabitants of high altitudes and in persons ascending 
in balloons. Marked excitement of the vascular system, hemorrhages, 
somnolence, weakness, vomiting, and similar symptoms are observed; 
in less marked cases a general excitement of the nervous system, sleep- 
lessness, etc., occur. These symptoms have been attributed to lack of 
oxygen, and compressed air and oxygen have been successfully used to 
combat them; but experiments show that the air-pressure may be as 
low as 400 mm. of mercury without interference with the respiratory 
exchange of gases. To a certain extent the symptoms are probably 
mechanical and due directly to the reduced pressure on the exterior. 
Recent studies show that the blood contains greatly increased numbers 
of red corpuscles in a given volume, and the percentage of hemoglobin 
is correspondingly increased. This is probably due, to some extent, 
to disturbance in the distribution of the corpuscles with stagnation in 
the peripheral vessels (see Diseases of the Blood). 

Insufficiency of Respiratory Air. — A certain amount of air is 
necessary for the continuance of health or life. Insufficiency may be 
due to diseases which obstruct the air-passages or affect the pulmonary 
tissue itself, and to foreign bodies (solid bodies, water in drowning) 
within the air-passages. Changes in the atmosphere or gases taken into 
the lung may cause insufficiency in the supply of oxygen, notably in 
CO-poisoning, in which the foreign gas enters into firm combination with 
the hemoglobin of the blood and thus excludes oxygen. 

The respiratory rhythm is maintained by the appropriate stimula- 
tion of the respiratory center by the appropriate mixture of carbon 
dioxid and oxygen in the circulating fluids. If, by repeated deep in- 
spiration, the amount of C0 2 in the blood decreases (called acapnia), 
there is no stimulation of the respiratory center and a condition of true 
apnea ensues. This view of apnea is maintained by some, while others 
claim that apnea may be induced after section of the vagus, and that, 
therefore, the gases in the blood are always responsible for apnea. 
This term should be used for the interruption of respiration due to the 
above causes, and not to cessation by mechanical or voluntary causes. 

Moderate decrease of the supply of air causes labored and rapid 
breathing, more or less cyanosis, depression, and stupor. This con- 
dition is termed asphyxia. Complete lack of air causes increase of these 
symptoms and death by suffocation. In these cases the blood is ex- 
ceedingly dark and fluid, and hemorrhages may be found in various situ- 
ations. The latter result from excessive blood-pressure during the 
death agony. Long-continued insufficiency of oxygen may directly 
or indirectly occasion degenerative diseases of the tissues. 1 

1 It, has often been asserted that anemia causes many of its symptoms and results 
because the blood is incapable of carrying sufficient oxygen in its reduced state. As 
a matter of fact, however, physiological experiments have demonstrated that the 
respiratory exchange (inhalation of oxygen and exhalation of carbonic acid gas) is 
but little affected and is as frequently increased as decreased. 



THE ETIOLOGY OF DISEASE 



29 



Electrical Influences. — The effects of powerful electrical currents 
and discharges on the tissues resemble those produced by burns. Locally, 
a dry, crisp, excavated lesion is produced. Later, hyperemia and ap- 
pearances resembling moist gangrene develop. The underlying muscles 
are more or less paretic. Changes in the blood-vessels and a fluid state 
of the blood, extending to some distance from the local lesion, have 
been observed. Very powerful and fatal discharges in some cases 
produce hemorrhages in the floor of the fourth ventricle and petechia? in 
the serous membranes and elsewhere. There are degenerations of nerve- 
cells, particularly in ganglia. Death seems to be caused by powerful 
inhibition of the heart. Lightning stroke leaves branching linear burns. 
Less powerful discharges, such as dynamo workers receive, cause sting- 
ing sensations in the absence of burns. If prolonged, there is loss of 
consciousness, depending for its depth upon the amount of and duration 
of the current. There is no definite amount that the body will always 
endure. 

Effects of X=rays. — Exposure of healthy or unhealthy tissues to 
x-rays causes cellular degenerations and necroses with secondary in- 
flammatory reaction. The skin — being most immediately exposed — ■ 
is the most susceptible of normal tissues; but diseased tissues and new 
growths are still more readily affected, probably because of their less 
stable condition. The point of severest attack is the nucleus of young 
specialized cells. The epithelial cells of the skin suffer first and most 
intensely; the glandular cells of the skin are less prone to degeneration. 
The damage to the skin by .r-ray is followed by a chronic dermatitis 
like xeroderma pigmentosum. This shows a tendency to go over into 
epithelioma. The .r-ray affects the hematopoietic organs by destroying 
the essential early leukocytes (karyorrhexis in the germ centers in lymph- 
tissue and reduction of the myelocyte series in bone-marrow). There 
is some basophilic degeneration and polychromatophilia of the erythro- 
cytes. X-rays may affect the genital organs by destroying the sperma- 
tozoa without producing physical impotence; by causing menstrual dis- 
turbances and abortion. After prolonged raying sexual gland atrophy 
may ensue. X-ray affects metabolism by increasing uric acid nitrogen 
and phosphorus excretion and by splitting body lecithin. Swelling 
and degeneration of the endothelial and other cells of the blood-vessels 
and thromboses may in part account for some of the results of .r-ray 
exposure. 

POISONS 

Definition. — The term "poison" may be applied to substances which 
when introduced in relatively small amounts into the living organism 
disturb its structure or functional activity. 

The Action of Poisons in General. — Gaseous poisons act primarily 
upon the respiratory mucous membranes with which they come in 
contact, or after absorption into the blood disorganize this fluid or lead 
to disturbances of the nervous system. Liquid poisons are generally 
absorbed through the gastro-intestinal mucous membrane, but may be 



30 



A TEXT-BOOK OF PATHOLOGY 



received directly into the tissues by injection under the skin. They 
are rarely absorbed through the skin. Solid poisons must in all cases 
first be dissolved, and are then absorbed like the liquid poisons. They 
may by their strong attraction for water absorb the latter directly 
from the tissues, and by this process alone may bring about important 
changes. 

The lesions due to a poison may be entirely local, as in the case 
of certain corrosives or caustics; in other cases the point of entrance is 
unaffected, the pathological manifestations being entirely due to the 
changes in different parts of the body, or to nervous disturbances result- 
ing from the circulation of the poison in the blood. Some poisons act 
immediately in destroying cells (caustics), while others must combine 
with them before the toxic effect is manifest; in other words, there is a 
latent period. 

The fate of poisons after ingestion is very different in different 
cases. Some poisons circulate with the blood and are eliminated un- 
changed. Others may suffer chemical change within the stomach or 
other cavities of the body before absorption, and may be either com- 
pletely neutralized, or may be converted into forms which are subse- 
quently slowly absorbed. After absorption into the blood other chemical 
reactions may occur, and the poison may be more or less neutralized, 
the system then suffering either from the resulting compounds or from 
the changed condition of the blood. Active destruction of the poison 
may occur in the blood or in the various organs, especially the 
liver. In these processes, however, the glandular organs may suffer 
seriously, various forms of degeneration or necrosis resulting. Cer- 
tain poisons, like the toxins, enter into chemical combination with 
cells of the body and remain fixed in this way. (For further details 
see Immunity.) 

The defense of the body against poisons lies in substances natural to 
it, and probably not increased in response to intoxication. This does not 
apply to the bacterial toxins in bacterial infection, but if injected in the 
absence of general infection some of the bacterial toxins may be de- 
toxicated as are inorganic or higher vegetable poisons. Among the 
defensive bodies are the blood, bile salts and acids, sulphuric acid as 
such or as sulphates, and the fatty acids. The processes at work are 
rapid elimination, oxidation, reduction, and hydrolysis. Poisons may 
be changed in form by precipitation or altered by combination with 
body proteins. 

The effect of poisons depends upon the dose as well as upon the 
nature of the substance, and also upon the individual. The repeated 
ingestion of certain poisons, such as arsenic or opium, may generate a 
considerable degree of immunity or tolerance (mithridatization). Simi- 
lar immunity may be a natural characteristic of a given individual or 
of classes or species. Susceptibility to the action of poisons is further 
influenced by age and constitutional vigor. Children bear certain 
poisons better, comparatively speaking, than adults, while the reverse 
is true of other substances. Sometimes there are idiosyncrasies which 



THE ETIOLOGY OF DISEASE 



31 



lead to peculiar results not observed in the average individual. In 
consequence of this, substances ordinarily not toxic may be extremely 
injurious to certain persons. (See Allergic) 

Sometimes poisons are comparatively innocuous when administered 
in one way, though powerfully toxic to the same animal when other- 
wise introduced. Thus in dogs intravenous injection of atropin is very 
slightly injurious, but injection of minute doses into the spinal cord 
causes rapid poisoning. Some experiments would indicate that the 
leukocytes are capable of fixing inorganic poisons and thus acting as 
defensive agencies. Non-fatal doses of poisons (arsenic) cause, first, 
diminution of the polymorphonuclear leukocytes, followed by leuko- 
cytosis; and the poison is found in abundance in these leukocytes. 
Fatal doses are unattended with the secondary stage of leukocytosis or 
the leukocytic fixation of the poison. These results need further con- 
firmation. 

In general, the action of poisons may be immediate destruction, 
stimulation to exhaustion and disintegration, or inhibition gradually 
to cessation of function. There are poisons with special predilection, 
e. g., strychnin for the nervous system; phosphorus for bone; snake- 
venom for blood, nervous tissue, and spleen. 

Elimination. — The excretion of poisons may take place through 
the kidneys, lungs, the mucous membrane of the gastro-intestinal 
tract, the mammary glands, or the skin. In some instances a poison is 
eliminated without change in the excreta; in other cases it suffers com- 
plete change, and is not present at all in the excretions. The rate of 
elimination varies greatly, and is more or less dependent upon condi- 
tions of the system. Some poisons, as phosphorus and mercury, may 
be stored up within the body for a considerable period, subsequently 
suffering slow elimination. 

Classification. — The number of substances which may act as poisons 
is very great, and the manifestations are of very different sorts. Classi- 
fication of poisons is, therefore, difficult and not entirely satisfactory. 
We may crudely distinguish between gaseous, liquid, and solid poisons; 
between animal and vegetable; organic and inorganic; but these classi- 
fications have no scientific value. 

From the point of view of the action of the poisons we may dis- 
tinguish corrosive poisons, or those which have a local action; organic or 
parenchyma poisons, or those which act less strongly at the point of 
application than upon the various organs to which they are conveyed 
through the blood; blood-poisons, or those which exercise their effects 
primarily upon the blood; and the nerve-poisons, or those which disturb 
the functional activity of the nervous system without producing de- 
finitely discoverable lesions. 

Corrosive Poisons; Escharotics; Caustics. — Under this heading 
are included various acids, alkalies, and mineral poisons, such as sul- 
phuric, nitric, oxalic, carbolic, and hydrofluoric acids, caustic potash 
or soda and ammonium, and gases like chlorin and bromin. Nitrate of 
silver, bichlorid of mercury, sulphate of copper, and other inorganic 



32 



A TEXT-BOOK OF PATHOLOGY 



compounds have a similar action, and certain organic bodies, such as 
cantharidin and croton oil, belong to the same class. 

All these poisons exercise a destructive effect upon the cells with 
which they come in contact, partly by abstraction of water and partly 
as a result of a coagulating power or similar action. The acids and 
mineral caustics usually produce dry and more or less discolored areas 
of necrosis; the caustic alkalies cause a sort of gelatinous change or a 
saponification of the tissue. The degree of injury depends upon the 
poison and the amount in contact with the tissues. There may be only 
a superficial injury of the outer layer of epithelial cells, or extensive 
destruction. Reactive inflammation is almost always present, and 
often, especially in the mucous membranes, the inflammatory reaction 
is extensive, though the corrosive action of the poison is limited in depth 
and extent. The affected part may present slight areas of necrosis with 
reactive hyperemia and inflammation beneath and around them, or 
deep eschars, vesicles, or large bullse. In the process of healing, extensive 
scars may form, and these may be serious in their effects, as in the case 
of strictures of the esophagus. 

Organic Poisons; Parenchyma Poisons. — This large group includes 
many metallic compounds that have a local corrosive or escharotic 
effect, but which may in smaller dose gain entrance to the blood and 
cause extensive organic lesions. It also includes poisons of vegetable 
origin and products of bacterial growth. In general, these poisons have 
a similar action. The kidneys and the mucous membrane of the intes- 
tines are especially active in their elimination and suffer most seriously. 
Degenerations of the epithelial cells of various sorts are met with, 
such as nuclear degenerations, coagulation necrosis, fatty degeneration, 
and even calcification. The changes may be diffuse or may occur in 
small foci. In the latter case small areas of granular appearance, 
having a lighter color than the surrounding tissues, are seen; and on 
staining the cells are found to color poorly or not at all, the nuclei often 
showing this change first. Nuclear degenerations (fragmentation, 
hyperchromatosis, etc.) are observed, and in some instances marked 
fatty degeneration of the cells occurs. Around the foci of degeneration 
there is more or less cellular infiltration (polymorphonuclear cells), 
and to a less degree the degenerated area itself is infiltrated. In cases 
in which diffuse change occurs there is equally diffuse round-cell infil- 
tration. After the acute process has subsided, hyperplasia of the con- 
nective tissues may occur and the affected part becomes more or less 
sclerotic or indurated. Regeneration of the parenchyma cells is less 
apt to occur. 

Some of the more important of the poisons of the group may now 
be separately considered. 

Phosphorus is a poison of considerable activity in the yellow form; 
the red variety is inert. Workmen in match factories are the most 
frequent victims of this form of intoxication, but occasionally accidental 
poisoning by swallowing occurs. In the latter the manifestations are 
acute. The pathological changes are catarrhal inflammation of the 



THE ETIOLOGY OF DISEASE 



33 



gastrointestinal mucous membrane and more or less widespread fatty 
degeneration of various tissues and organs. The liver suffers most 
severely, being enlarged, light yellow or reddish in color, and friable or 
doughy. Microscopically, the liver-cells are found extensively de- 
generated (fatty). Similar but less marked fatty degeneration is 
found in the renal tubules, gastro-intestinal epithelia and heart-muscle, 
and in the intima of the blood-vessels. Extensive jaundice is frequent 
and numerous hemorrhages may occur. In the more chronic poisoning 
of match-makers the poison enters through the mouth and respiratory 
passages, being inspired as dust. Chronic catarrhal inflammation of the 
respiratory tract may occur and a peculiar form of necrosis of the 
bones (see Bones) is met with. 

Arsenic is poisonous in certain forms (white arsenic, arsenous 
acid) and inert in other forms (the sulphids). Acute poisoning occurs 
when toxic forms are swallowed in large doses; the chronic forms of 
poisoning result from gradual ingestion or the inhalation of dust con- 
taining arsenic. Cases of the latter sort occur when wall-paper, hang- 
ings, and the like, colored with arsenic pigments, are used. The lesions 
in acute arsenic-poisoning resemble those produced by phosphorus. 
The gastro-intestinal inflammation is, however, more severe; while the 
fatty degeneration of the organs is less marked. In chronic arsenic- 
poisoning changes in the peripheral nerves (degeneration and inflam- 
mation) are most important. It is likely that focal or diffuse myelitis 
may likewise be caused by this poison. Chronic inflammations of the 
gastro-intestinal or respiratory mucous membranes are met with in 
some cases. Inflammatory lesions and pigmentation of the skin may 
occur. 

Lead. — Among the compounds leading to acute or subacute poison- 
ing the chromate, the acetates, the carbonate, and oxid are most im- 
portant. Chronic poisoning occurs in workmen in paint manufactories 
and among type-setters and painters, and in persons drinking certain 
waters that have been conducted through lead pipes. Less rarely the 
use of cosmetics, dyestuffs, etc., containing lead causes chronic poison- 
ing. In the acute forms of lead-poisoning moderate gastro-enteritis 
occurs. In the chronic form changes in the nervous system are most 
important. Peripheral neuritis is the most frequent lesion, but changes 
in the large ganglionic cells of the gray matter of the cord have some- 
times been found. Diffuse sclerosis of the blood-vessels, interstitial 
nephritis, and the lesions of gout may be present. Atrophy and fatty 
degeneration of the muscle-fibers are less important results. A blue line 
on the gums at the junction with the teeth (due to deposit of sulphid 
of lead) is a lesion of clinical importance. A constant and diagnostically 
suggestive change is found in a peculiar degeneration (basic degenera- 
tion) of the erythrocytes. (See chapter on Blood.) 

Mercury. — Poisoning with mercury may be acute, subacute, or 
chronic. The first is due especially to the corrosive chlorid and other 
mercuric salts; the second, to calomel or small doses of those of the 
former group. Chronic poisoning occurs as a result of inhalation of 

3 



34 



A TEXT-BOOK OF PATHOLOGY 



fumes or dust containing mercury, and is seen in workmen in mirror 
manufactories. In the acute cases violent inflammatory and necrotic 
lesions of the gastro-intestinal tract are seen. Parenchymatous de- 
generation, fatty change, and even calcification of the renal epithelium 
may occur; and fatty degeneration in other organs may sometimes be 
met with. In subacute cases marked by ptyalism some change is doubt- 
less present in the salivary glands, but the nature of this has not been 
determined. 

Ergot is a poison capable of producing intense toxic results. 
It contains two important toxic principles, sphacelinic acid and an 
alkaloid, cornutin. Acute poisoning sometimes results from over- 
dosage; while chronic intoxication occurs from the use of affected grain, 
particularly in famine years. Widespread poisoning of communities 
has sometimes resulted. The lesions produced are not definite or uni- 
form. Gastro-intestinal inflammation and erosion of the mucous mem- 
brane have been observed, but are not constant; sclerotic change in 
the spinal cord has been found in a few cases. Gangrene is a frequent 
lesion, probably resulting from vascular obstruction due to contrac- 
tion of the blood-vessels. Enlargement of the spleen has sometimes 
been noted. 

Toxalbumins from Plants. — Certain vegetable bodies, like ricin, de- 
rived from the castor bean, and abrin, derived from jequirity bean, are 
exceedingly toxic, acting in part as blood-poisons, but also as parenchyma 
poisons. Injected into animals these substances cause violent intoxica- 
tion and focal areas of necrosis in various situations, notably in the 
liver. In part these lesions result from vascular thrombosis; in part, 
from direct action. The study of the action of these poisons is of par- 
ticular interest from the resemblance of the lesions to those caused by 
certain bacteria and bacterial poisons. 

Toxic Products of Bacteria. — In the growth and multiplication of 
various bacteria definite toxic substances are created, and through the 
latter the lesions of infection are to a large extent produced. Such 
poisonous bodies may be generated in the growth of the bacteria out- 
side of the body, as well as within the body. In the latter case the 
pathological lesions at the point of infection may be the focus of origin 
of toxic substances which are then distributed throughout the body. 
This is eminently true of tetanus and, to a large degree, of diphtheria. 
In other cases the bacteria themselves are transported to various parts 
of the body and, finding lodgment in the tissues, set up changes by 
which their toxic products are evolved. The latter increase the local 
foci of pathological change and then spread in the circulation and cause 
general intoxication. Further reference to these poisons will be made 
when discussing the individual bacteria. 

The venom of serpents and of various insects contains toxic bodies, 
some of which are albuminous in nature. These vary in their action, 
being to some extent blood-poisons, but more particularly parenchyma 
poisons. The lesions produced are local and general. Locally, there are 
intense inflammatory reaction and edema around an area of cellular 



THE ETIOLOGY OF DISEASE 



35 



necrosis or destruction where the poison has come in immediate con- 
tact with the tissues. The blood seems to suffer great disorganization 
and corpuscular change. Petechial hemorrhage and foci of cellular 
necrosis occur in various organs, and edema of the lungs is frequently 
present. The action of the venom of different animals varies in kind 
and intensity to a certain extent, but is, in general, of a similar type. 
Snake-venom has the. peculiarity of setting up immunity reactions 
similar to those induced by bacterial toxins. It contains several differ- 
ent fractions, those toxic to blood, nervous tissue, kidney, etc. 

Blood-poisons. — Various liquid or gaseous substances are termed 
"blood-poisons" because of their especial action upon this tissue. The 
blood-poisons may be classified as (a) those which combine with the 
hemoglobin without changing the corpuscles; (b) those which alter the 
red corpuscles and the coloring-matter ; (c) those which affect the blood 
as well as the tissues generally; (d) those which cause changes in the 
blood-plasma, increasing or decreasing the tendency to clotting; and (e) 
those which destroy leukocytes. 

(a) Among the poisons which act by entering into combination 
with the hemoglobin without changing the corpuscles, carbon monoxid, 
cyanogen, and hydrogen sulphid are important. In carbon-monoxid 
poisoning, which often results from inhalation of the fumes of charcoal 
burning with insufficient air, the blood has a light color and light pete- 
chial discolorations may be seen in various parts of the body. In cyano- 
gen-poisoning the blood is similarly light in color; while in H 2 S-poisoning 
the blood is often dark, sometimes quite black. 

(6) Among the poisons which disorganize the blood-corpuscles and 
later the hemoglobin are a large number of chemical agents used in 
medical practice or in the arts, including potassium chlorate, nitro- 
glycerin, anilin, nitrobenzol, various coal-tar derivatives, and arseni- 
uretted hydrogen. Certain poisonous plants (toadstools) act similarly. 
These poisons lead to a reduction of the hemoglobin with formation of 
methemoglobin and at the same time destruction of the corpuscles 
themselves, with release of the hemoglobin into the serum. The altered 
condition of the blood often induces secondary changes, such as fatty 
degeneration and hemorrhages in various organs. The blood-corpuscles 
are found in variously degenerated conditions, showing microcytosis 
and poikilocytosis in particular. Nucleated red corpuscles may be 
present as in other conditions of blood destruction with attempted 
regeneration. 

(c) Among the poisons which disorganize the blood and at the same 
time cause changes in the parenchyma of organs, reference has been 
made to abrin and ricin. In addition to the organic changes, these 
substances cause certain alterations in the blood itself, increasing the 
coagulability and thus inducing thrombosis. 

(d) Various substances introduced in sufficient quantity are capable 
of affecting the plasma of the blood or the corpuscles in such a way as 
to affect its coagulability. Calcium salts, carbonic acid gas, and fibrin 
ferment are active in this way, but the last alone produces toxic results 



36 



A TEXT-BOOK OF PATHOLOGY 



through this function. Ferment intoxication may occur in consequence 
of various other intoxications, when corpuscular or tissue destruction 
has liberated the ferment. Among the poisons which decrease coagula- 
bility peptone (albumose) is important. 

(e) Saponin and benzol destroy leukocytes. 

Injection of large quantities of water or hypotonic salt solution may 
have a hemolytic effect. 

The blood-serum of one individual may contain hemolytic agents 
for the cells of another person, and more frequently for those of another 
species 

Nerve-poisons. — This group contains a large number of substances 
capable of producing violent symptoms and even death without definite 
change in the tissues of the body. Certain investigations showing cer- 
tain alterations in the finer structure of the nervous system in disease 
and in cases of intoxication suggest that histological changes in the 
central neurons may be found to result from poisoning by these sub- 
stances. Changes of this kind (changes in size and form of the cell and 
nucleus, thickening, contraction, or disappearance of dendrites, altera- 
tions in the chromophilic bodies, etc.) have been described in the gray 
matter of animals poisoned with alcohol and certain toxins of bacterial 
origin. It is not unlikely that similar changes will be found in other 
conditions. Among the nerve-poisons are alcohol, chloroform, ether, and 
various alkaloids like morphin, atropin, etc. In this same group might 
be included some of the poisons contained in the venom of serpents and 
other animals, but these usually cause definite lesions in the blood or 
tissues of the body. 

Ptoviain Intoxications. — Another group of poisons with action similar 
to the last are those produced within the body by putrefactive action 
or in various foodstuffs before ingestion. Frequently cases have been 
observed in which all the members of a family or even large numbers 
of people have been poisoned by eating certain meats, sausages, ice- 
cream, and other foods. In some of these cases it has been found that 
the toxic element was a basic compound resembling the alkaloids 
in chemical structure. To these putrefactive compounds the name 
ptomain is given. One of these compounds, which occurs in cheese, and 
occasionally in milk, has been termed "tyrotoxicon." Intoxications of 
this class must be distinguished from infections resulting from the use 
of food contaminated with micro-organisms. The symptoms may be so 
rapidly developed (absence of incubation period) and so immediately 
generalized that the distinction can be arrived at clinically, but the 
absolute diagnosis is made bacteriologically. (See p. 37.) 

These conditions in food are usually set up by anaerobic bacteria. 
The pathological results are paresis of the centers of special sense, de- 
generation of ganglion cells, and hyperemia of all organs. The intoxica- 
tions usually arise from the intestinal tract and are due to changes in 
meat by bacteria present in the slaughtered animal before death. 
The poison is thermostabile and does not affect the appearance or odor 
of meat and may not change the flavor. The symptoms are vomiting, 



THE ETIOLOGY OF DISEASE 



37 



colic, and diarrhea, followed by collapse. The active agents are bac- 
terial products in the meat, but which can also be obtained by growth 
of the same organisms in vitro. It is an intoxication and not a bacterial 
infection. Bacillus enter itidis of Gartner is the most important single 
organism in this group. 

A considerable number of ptomains have been separated, includ- 
ing neurin, obtained from putrid flesh; muscarin and ethylendiamin, 
derived from decayed fish; mydalein, and mydatoxin. Some of these 
substances produce toxic results indistinguishable clinically from those 
produced by certain alkaloids. This fact has become one of great 
importance in medicolegal investigations. 

VEGETABLE AND ANIMAL PARASITES 

Vegetable parasites are by far the most important causes of dis- 
ease. The belief in a living cause or contagium vivum is by no means 
a recent acquisition, but the actual demonstration that diseases may be 
caused by minute living organisms has only recently been reached. 
The micro-organisms in question (bacteria) belong for the most part 
to the vegetable kingdom and constitute the lowest orders of fungi. 
Their biological characters and their relations to special diseases will 
be described in a subsequent chapter. 

Etiological Relationship of Bacteria to Disease. — It is difficult to 
prove the specific relation of bacteria to disease. Koch has laid down 
four important laws which must be conformed with before the etiologi- 
cal role of a bacterium is admitted. These are: (1) The bacterium 
must be found in the diseased person; (2) it must be cultivable upon 
media outside the body; (3) pure cultures introduced into a healthy 
animal must produce the disease in the animal; and (4) the bacterium 
must be recoverable from the body of the animal. In a number of dis- 
eases micro-organisms have been proved to be the specific causes 
according to the requirements of Koch's rules. In other diseases it has 
not been possible to furnish absolute proof, though the presumptive 
evidence, furnished by constant occurrence of the bacteria, suggestive 
association with the lesions of the disease, absence of the bacteria in 
other diseases, etc., is sufficient to satisfy all but the most skeptical. 

Classification of Diseases Due to Bacteria. — The general term 
infectious disease is applied to all such as are caused by bacteria. In 
some cases the diseases are readily communicated from person to person, 
even though contact has not been immediate. These are termed con- 
tagious diseases, while the term non-contagious is given to those in which 
such ready transference is not observed. As a matter of fact, the dis- 
tinction is artificial. Any infectious disease may be communicated 
from the diseased to the healthy if the germs or bacteria are transferred. 
In some diseases this transference readily occurs, even through the air 
and at considerable distances; in others actual contact is necessary; 
while in still others secretions or excretions of the diseased must be con- 
veyed to the healthy. Contagiousness is, therefore, a matter of degree 



38 



A TEXT-BOOK OF PATHOLOGY 



only. It is better to use the terms communicable or transmissible dis- 
eases for those in which every case is dependent upon a preexisting one, 
the mode of transmission being either direct or indirect. Malaria is an 
indirectly transmissible disease requiring the intervention of the mos- 
quito, while diphtheria is a directly communicable infection, no agent 
being required for its spread. 

Infectious diseases may at times spread in communities, affect- 
ing large numbers of people. Such a dissemination is termed epidemic, 
and the disease an epidemic disease. When the disease spreads over 
large areas, as a whole country or continent, the term pandemic dis- 
ease is applied. Other infections are constantly present in a locality; for 
such the terms endemic and endemic disease are used. Some endemic 
diseases are restricted to certain localities and seem in some measure 
dependent upon local conditions (of atmosphere, soil, etc.) for their con- 
tinuance. These are called miasmatic diseases. The soil, etc., have, of 
course, nothing directly to do with disease, but merely afford the con- 
ditions necessary for the propagation of the infecting agent, as, for 
example, swamps and the malarial mosquito. 

Infectious diseases are frequently described as local or general. 
Local infections are those that present specific pathological change in a 
restricted part of the body; the general organism suffers more or less in 
consequence. Examples of this are erysipelas and diphtheria. General 
infections are marked by an immediately generalized disease, as in 
typhus fever or plague. Strictly speaking, most if not all of the so- 
called general infections are at first local. Among purely local infec- 
tions might be named the diseases of the skin due to vegetable micro- 
organisms. 

Entrance of Micro-organisms into the Body. — Bacteria may be 
inhaled or swallowed, may enter through abrasions in the mucous 
membrane or skin, and may be transfered in utero from the maternal 
to the fetal blood. The mode of entrance in individual diseases de- 
pends upon the nature of the bacterium, its habitat, and surrounding 
conditions. Some may enter in but one way; others gain access in any 
of the different ways. Details regarding this subject will be given in 
the discussion of special infections. 

Animal parasites of various kinds act as causes of disease. This 
group of diseases is termed the parasitic diseases or invasion diseases. 
In some instances microparasites cause a clinical course similar to that 
of infectious diseases (malaria, dysentery, trichinosis) ; in other cases the 
manifestations bear little resemblance to infections. 



CHAPTER II 



DISORDERS OF NUTRITION AND METABOLISM 

Food. — In the life of the organism certain substances are needed 
for growth, for the repair of tissues consumed in the wear and tear of 
life, and to supply heat and other energy. Among these foods are 
proteins, carbohydrates, fats, inorganic salts, and water. A continuance 
of normal existence requires more or less definite proportions of the first 
three and at least a sufficiency of salts and water. The amount of food 
and the exact proportions vary somewhat in individual cases and under 
varying circumstances. Voit, the pioneer in this work, found that a 
laboring man under ordinary conditions requires 118 gm. of protein, 
56 gm. of fats, and 500 gm. of carbohydrates. This diet contains 
3055 calories. Recent studies all tend to show that the amount of 
protein is excessive and that some reduction of Voit's figure is desirable, 
though the low protein figures of Chittenden and others err on the other 
side. The minimum figure is perhaps from 60 to 70 gm. The weight of 
the individual and the amount of the daily work must determine the 
requisite diet, 35 calories per kilo of weight being an average figure for 
a man doing light work. The proteins of the diet are necessary to 
restore tissue waste, since the organism cannot build up proteins from 
simpler compounds. This consumes part of the nitrogenous foodstuffs. 
The rest, with most of the fats and carbohydrates, is mainly useful in 
contributing energy. 

Diminished Supply of Food; Inanition; Starvation. — Either 
the want of food or diseases of the digestive organs with lack of ab- 
sorption may lead to insufficient nourishment. This causes a loss of 
body weight, as the necessary heat-producing and energy-giving sub- 
stances must be supplied to maintain life, and the tissues are consumed 
for this purpose. During the first two to five days of starvation in 
previously well-nourished persons the glycogen supply of the body is 
largely consumed, and the amount of protein consumption is corre- 
spondingly less than on subsequent days. In prolonged starvation the 
average requirement of from 28 to 32 calories per kilo has been found 
quite constantly, and with like constancy about 13 per cent, of this 
energy is supplied by protein and 87 per cent, by fat. In fat persons or 
animals the amount of protein consumption is relatively less than in 
those less supplied with fat. Toward the end of long fasting periods the 
nitrogen elimination falls to low figures. At the same time the urea- 
nitrogen is especially reduced, partly on account of the reduction of 
exogenous proteins in the metabolism and partly on account of acidosis. 
(See Acid Intoxication.) The subcutaneous and other fat depots suffer 
first in the emaciation of starvation ; later, the glandular organs, muscles, 

39 



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A TEXT-BOOK OF PATHOLOGY 



nervous system, bones, and heart. The chlorids in the urine are regu- 
larly diminished, while calcium salts are increased in correspondence 
with the destruction of osseous tissue. 

The functions of various organs suffer greatly: the respirations and 
heart action are weak, muscular exertions are reduced to a minimum, 
the endurance and nervous force decline, the body temperature sinks, 
and finally death may occur from exhaustion or secondary affections 
consequent upon the disturbed nutrition. (See Acid Intoxication.) 
The blood in starvation preserves its chemical constitution and corpus- 
cular richness surprisingly, even after prolonged abstinence. There is 
probably a reduction in the total mass of blood. 

Increased Supply of Food; Overfeeding. — The effect of this 
depends upon individual conditions, such as the amount of exercise, 
the surrounding temperature, and less easily demonstrable peculiarities 
of the individual. An excess of protein food leads to increased excretion 
of the end-product of its metabolism — urea. Experiments have shown 
that to a slight extent a reserve amount of albuminous tissue may. be 
built up by excess of protein food. Great excess of protein eventually 
disturbs digestion and leads to its own discharge with the feces. 

The carbohydrates and fats are broken up in the body and excreted 
mainly as carbonic acid and water. An excess of these foods tends to 
cause increased deposition of reserve fat and glycogen, which may be 
called upon at subsequent times of need. This deposition is a normal 
or physiological process and has the distinct purpose just indicated. 
Exceptionally in the condition called obesity the storing up of fat is 
inordinate and probably pathological. 

Metabolism of Fat. — The fat of the body has two sources: the fat 
of the diet and sugar either ingested or made within the body. In the 
case of ingested fats the deposited fat is of like composition, and may, 
therefore, be widely different in its composition from the fat peculiar 
to the species; in the case of fat made from sugar it is always specific 
for the species. Thus, a dog fed upon mutton fat deposits mutton fat in 
his tissues, while in making fat from sugar fat peculiar to his species and 
differing from mutton fat is deposited. The sugar from which fat is 
built up may be ingested as such or may be derived from the carbo- 
hydrates, fats, or proteins of the diet or tissues. 

Causes of Obesity. — Excessive ingestion of food by persons having 
active digestion and leading sedentary lives may occasion unusual depo- 
sition of fat. It is difficult, however, to determine the limits between 
physiological and pathological fatness. In some cases patients assert 
that the amount of food has not been excessive, and this may be actually 
true. Obesity in such individuals is undoubtedly pathological and due to 
some inherent abnormality of metabolism. A further proof of the ex- 
istence of such a tendency is seen in certain families in which excessive 
fatness is common, even in childhood. The nature of this metabolic 
disorder is obscure. It has often been held that the power of oxi- 
dation is lacking, and, as a matter of course, the amount of oxygen 
consumed is deficient in comparison with the amount of food ingested. 



DISORDERS OF NUTRITION AND METABOLISM 



41 



This must be true or the fat could not accumulate; but it remains to be 
shown whether the diminished oxygen consumption is the primary 
cause or only an incident in the disease. Experimental investigations 
have shown that the basal heat production (that exhibited by the 
normal body when fasting and with the external temperature at 37° C.) 
is not exceeded in a downward direction in obesity, though the figure 
may be consistently low in this condition. The explanation of this 
circumstance may be found in the fact that in fat persons equivalent 
weights represent an undue amount of inactive (adipose) tissue, and 
that large deposits of subcutaneous fat afford an external protection 
against loss of heat; consistently low figures of heat requirement may, 
therefore, indicate, if not pathological, at least continuously low, oxida- 
tion; and it is possible that the methods of observation and the range of 
error of these methods may prevent the detection of slight deficiencies in 
oxidation that in the long run (over periods of weeks or longer) could 
explain fatty accumulations. 

Some experiments seem to indicate retardation of oxidation though 
no actual reduction. 

Pathological Anatomy. — The excessive adipose tissue in this condi- 
tion is found in the skin and subcutaneous tissues, in the omentum and 
peritoneum, around the kidneys, heart, and mediastinal tissues, in the 
liver, and less commonly elsewhere. The amount varies from slight 
excess to monstrous deposits. Secondary changes in the organs (not- 
ably the heart muscle) may be due to pressure or functional inactivity. 

Associated Conditions. — Fatness is more or less closely related to 
certain other diseases of metabolism, such as diabetes and gout. Anemia 
is frequently present and has sometimes been regarded as a cause, 
operating by reducing oxidation. 

The occurrence of fatness in certain types of nervous disease, such as 
hysteria and idiocy, suggests a nervous perversion of fat metabolism, 
though possibly other conditions, for example, disease of the glands 
of internal secretion, may be fundamentally involved. It is well known 
that castration and the menopause are frequently followed by in- 
crease of fat, and certain diseases of the hypophysis and thyroid are 
likewise attended by obesity. There may or may not be manifest 
nervous symptoms in these cases. 

Excessive Tissue Destruction. — This has been referred to in con- 
nection with inanition; but it may be independent of the amount of 
food ingested. Among the conditions in which this is observed may 
be mentioned fever, infectious or of other forms; chronic infectious 
diseases, with or without fever; tumors, especially carcinoma; intoxica- 
tions of various sorts; some cases of Graves' disease, etc. In all of these 
conditions the fats of the body may waste as in simple inanition; but 
there is an early and marked tendency to consumption of the more 
important protein structures. 

The nature of the metabolic disturbances in these cases is obscure, 
though it is likely that toxic substances of various sorts are the direct 
causes. This is most probable in the case of direct intoxications (phos- 



42 



A TEXT-BOOK OF PATHOLOGY 



phorus), but is also likely in other cases. In Graves' disease and car- 
cinoma, as well as in fevers, there are doubtless poisonous substances 
in the blood, but whether these are the causes of the metabolic changes 
or not requires further study. The fact that thyroid extract is capable 
of causing excessive destruction of tissue in normal or obese persons is 
significant in this connection. 

Acid Intoxication. — In the final metabolic transformation of pro- 
tein there are produced ammonium, urea, kreatinin, and other nitrog- 
enous substances. The formation of urea is still obscure in some par- 
ticulars. It is certain that a large part is produced in the liver and 
some is formed in the glandular organs. The intermediate steps in the 
manufacture of urea have not been definitely determined, but it is 
known that the liver is capable of converting ammonium salts directly 
into urea, and it is probable that ammonium is an important inter- 
mediate product of protein transformation. An excess of acids in the 
body (either from introduction from without or production in the 
body) is in part neutralized by alkaline bases in the blood and tissue 
juices and in part by ammonium. In consequence of this consump- 
tion of ammonium the urea of the urine decreases and the ammonium 
salts are increased. The quantity of such salts is, therefore, in a measure 
an indication of the condition which has been termed "acid intoxica- 
tion." When the fixed alkalies (sodium and potassium) are more or less 
exhausted in the neutralization of acids, symptoms of acid intoxication 
result. Fortunately, this is usually prevented by the abundance of 
ammonium, but in extreme cases of acid intoxication the ammonium 
does not suffice. 

Experimental acid intoxication is easily produced in animals by 
feeding them with foods deprived of alkaline bases or by direct ad- 
ministration of acids. In the former case the acids (sulphuric from the 
sulphur of albuminous food, and phosphoric from the phosphorus) 
resulting from transformation of food and tissues must be neutralized 
by the alkalies of the body and the ammonium incidental to the process 
of urea formation in the liver; in the latter case there is direct excess of 
acid. Such acid intoxication is readily produced in herbivorous animals, 
as the amount of protein food is small, and in consequence but little 
ammonium is produced. Various nervous symptoms are observed. 
The animal breathes quickly, the pulse grows rapid, muscular weakness, 
ataxia, and tremor develop, and finally coma or collapse terminates 
the disease. The administration of alkalies may completely arrest the 
progress of the condition and full restoration may occur. 

Acid Intoxication in Man. — Somewhat similar symptoms are seen 
in man in certain diseases in which increased elimination of ammonium, 
with decrease of urea and the excretion in the urine of certain organic 
acids, have been discovered. The assumption is warranted that these 
are cases of acid intoxication. 

Etiology. — Among the conditions in which this occurs are fever, 
diabetes, carcinoma, acute yellow atrophy of the liver, narcosis, severe 
anemia, phosphorus-poisoning, advanced gastro-intestinal disease, 



DISORDERS OF NUTRITION AND METABOLISM 



43 



and inanition. Sometimes no discoverable cause can be detected 
(cryptogenic acid intoxication). Gastro-intestinal disorders are very 
possibly the occasion of this form of obscure acidosis. Poisons pro- 
duced in the intestines may, perhaps, set in play the metabolic dis- 
turbances which terminate in overproduction of acids. 

Among the acids concerned are lactic, sarcolactic, sulphuric, phos- 
phoric, diacetic, and beta-oxybutyric. These in part combine with the 
fixed alkalies and with ammonium, and in part are excreted as such. 
Some, as sarcolactic acid, usually suffer decomposition in the body, and 
are, therefore, rarely met with in the urine. The important acids are 
oxybutyric and diacetic, and with these is frequently combined 
acetone. 

The ketonic acids, beta-oxybutyric and aceto-acetic, are now 
known to be due to the combustion of fat. In normal catabolism of 
fat there is first a cleavage into glycerol and fatty acids. The for- 
mer is converted into sugar; the latter oxidized in successive stages 
until the higher acids are converted into butyric acid. At this stage 
the process of oxidation becomes somewhat changed, and beta-oxy- 
butyric acid, aceto-acetic acid, and, finally, through acetic and formic 
acid, the end-products (carbon dioxid and water) are produced. At 
the stage of aceto-acetic (diacetic) acid a side reaction occurs whereby 
acetone is formed. Normally this occurs to the extent of traces only, 
but when fat is burned in large quantities the acetone formation in- 
creases considerably beyond the proportionate increase of the fat con- 
sumption. In diabetes and sometimes in other conditions in which 
considerable fat consumption takes place, either as a result of the ex- 
cess of fat catabolism or from failure of certain fermentations con- 
cerned, the conversion of beta-oxybutyric acid and aceto-acetic acid 
into acetone is halted or diminished and the blood is flooded with the 
ketone acids, which then act injuriously by abstracting bases from the 
tissues or as direct poisons. 

There is always reduction of oxidation in cases of acid intoxication, 
but it is not known whether this is the primary disturbance or whether 
it is but an accompaniment. Experimentally it has been shown by 
several observers that diminution in the supply of oxygen will lead to 
increase of these acids. They owe their presence to excessive production 
and to the failure of the normal oxidation. Other substances may 
result from protein destruction with insufficient oxidation. Among these 
are the amino-acids, leucin and tyrosin, as well as lactic acid, found in 
the urine in phosphorus-poisoning and acute yellow atrophy of the 
liver as well as in other conditions. 

The symptoms of acid intoxication in man may be quite similar 
to those seen in experiments upon animals. Marked dyspnea (air 
hunger), rapidity of the pulse, depression, stupor, and deep coma (coma 
carcinomatosum ; diabeticum) are some of the more pronounced mani- 
festations. The explanation of the symptoms occurring in acid in- 
toxication is not entirely clear. The extreme dyspnea, which is one of 
the most characteristic symptoms, was first naturally referred to as- 



44 



A TEXT-BOOK OF PATHOLOGY 



phyxia; but as it has been found that the blood contains an adequate 
amount of oxygen and a greatly diminished quantity of C0 2 , this ex- 
planation cannot hold. It is probable, however, that the dyspnea is 
due to the inability of the blood to carry off carbon dioxid from the 
cells, in consequence of the reduction of available alkali owing to its 
fixation by the acids. There is thus a decrease of oxidation from the 
accumulation of carbon dioxid in the cells, but not asphyxia in the 
ordinary sense of the word. Some have believed that the symptoms 
of acid intoxication are due to certain as yet unknown toxins which 
are produced at the same time as the acids. There is no direct proof of 
this, and the evidence at hand would indicate that the acids in them- 
selves, by reducing the available alkaline bases of the blood and by dis- 
turbing the metabolic processes in the cells, are sufficient to cause the 
symptoms. 

Disorders of Protein Metabolism. — Proteins are complex bodies 
made up of combinations of various amino-acids in proportions differ- 
ing widely in the proteins of the various tissues of the body and in those 
of different species. Within the gastro-intestinal tract the digestive 
ferments convert proteins into proteoses and peptone, and finally into 
the constituent amino-acids. There are thus set free the elements 
from which reconstruction of proteins of composition characteristic 
of the species in question can be effected. Some of the amino-acids 
from the foreign protein of the food may be unsuitable for the recon- 
struction of these new proteins, while some may be present in super- 
fluous amount. These fractions are catabolized and excreted in the 
form of end-products. The major part is used for the resynthesis of 
protein. This was until recently thought to occur exclusively in the 
wall of the intestine, so that there should be delivered into the blood 
re-formed proteins similar to those of the blood. More recently it has 
been learned that the amino-acids are absorbed, in part at least, into 
the blood and utilized for rebuilding of new protein in the liver or other 
tissues. During youth and the growth period and after exhaustive 
wasting of the tissues considerable portions of the food proteins may 
be utilized directly for the upbuilding of the tissues. At other times 
only a small portion is thus utilized to repair the waste of cells and to 
replace dead cells. The greater part of protein food is quickly catab- 
olized and excreted. The level of protein content of the blood is 
maintained very tenaciously, and in case of starvation the blood ab- 
stracts proteins from the cells to maintain the level, while as a result 
of overfeeding some of the protein is deposited as a storage within cells, 
while the larger part is quickly catabolized. There is no capacity for 
storage of protein comparable to the storage of carbohydrates, as glyco- 
gen in the liver and muscles, or of fat in the various areolar tissues. 

The catabolism of proteins is exactly comparable to their digestion 
in the intestinal tract, but takes place within the cells under the influence 
of endotrypsin. First proteoses and peptone are formed, then amino- 
acids, and, finally, end-products varying somewhat with the source 
of the protein involved. The exogenous proteins, those derived directly 



DISORDERS OF NUTRITION AND METABOLISM 



45 



from food, are mainly excreted as urea and ammonium; the endogenous, 
those of the tissues of the body, when eatabolized yield only small 
portions of the urinary urea and ammonium, and those of the muscles 
in particular are excreted as creatinin. The latter substance is derived 
from the creatin of muscles, which in turn is probably an anabolic 
product of amino-acids made by a special muscle metabolism. 

In the normal man excess of protein feeding is speedily followed by 
marked increase of elimination of the end-products, urea and ammo- 
nium. Only a fractional retention occurs. In certain pathological con- 
ditions, such as nephritis and gout, considerable nitrogen retention may 
occur, especially in the form of non-protein nitrogenous bodies. In 
fasting and starvation the nitrogenous elimination falls to very low 
levels, in which the exogenous nitrogen end-products (urea and am- 
monium) are specially affected. The amount of creatinin is maintained 
at a quite fixed level, being reduced only to the extent of the subtrac- 
tion of the relatively small amount of creatinin derived from the meat 
and meat extracts of diet. 

Under conditions of rapid catabolism of protein, such as in leu- 
kemia, carcinoma, and internal suppurations, the proteoses and peptone 
may be liberated in such quantity as to be in part excreted in the urine 
(proteosuria, peptonuria, albumosuria). These proteoses and peptones, 
however, being derivatives of native protein, are non-toxic, contrasting 
with the toxic proteoses and peptone derived from foreign proteins in 
the digestive tract. Whether or not any of the latter are absorbed into 
the blood and excreted in the urine in pathological conditions is un- 
certain. In certain other conditions of rapid protein catabolism (as 
in autolytic destruction of liver substance — acute yellow atrophy, phos- 
phorus-poisoning, etc.) amino-acids may be excreted in the urine. 

In the catabolism of protein, under conditions in which the utiliza- 
tion of carbohydrates is greatly reduced, as in diabetes, considerable 
sugar may be an end-product. This is derived from the amino-acids, 
which lose their NH 2 by a process of deaminization and yield oxy- 
fatty acids, which are finally converted into dextrose. This process ac- 
counts for much of the persistent dextrosuria of severe cases of diabetes 
after the glycogen storage has been exhausted and the diet has been 
deprived of all carbohydrate matter. 

Creatinin elimination in the urine may be utilized as an indication 
of the state of muscle metabolism. In cases of rapid muscular waste 
from fever or other causes an excessive output of creatinin is met with; 
and in certain extreme cases creatin itself — the substance in muscle 
from which creatinin is derived — is thus excreted, probably as an ex- 
pression of failure of conversion into creatinin. In muscular dystro- 
phies the elimination of creatinin may be decreased. 

Disorders of Purin Metabolism. — By purin metabolism is meant 
the metabolism of cellular nuclei. The nuclei contain nucleoproteins 
which are combinations of globulin and nucleic acid, the latter being com- 
posed of phosphoric acid, pentose-sugar, and a base, either purin or pyrim- 
idin. The important purin bases are the aminopurins, adenin and guanin, 



46 



A TEXT-BOOK OF PATHOLOGY 



and the oxypurins, hypoxanthin and xanthin. In the normal purin ca- 
tabolism there is first a separation of the globulin and nucleic acid, and 
then, under the influence of special enzymes, the latter is broken up into 
its components and the purin bases deaminized and oxidized to uric 
acid. In the final urinary excretion both purin bases and uric acid are 
present, so that the catabolism does not wholly proceed to the end- 
product. Under ordinary conditions of diet the urine contains more 
purin of exogenous than of endogenous origin. The foods that yield 
this are such cellular gland foods as thymus, pancreas, liver and kidney, 
and, to a less extent, muscle (meat); leguminous vegetables; and coffee, 
tea, and cocoa. On a purin-free diet the excretion falls to a low level of 
fair constancy. Apparently the exogenous purins are excreted in toto, 
no part being utilized in the anabolism of nucleic acid. To a certain 
extent uric acid is oxidized in the body to form urea and is excreted as 
such. 

Under normal conditions the blood contains from 0.5 to 1.0 mg. of 
uric acid in 100 c.cm. Under certain circumstances this quantity may 
rise to 8 or 10 mg. either temporarily or for longer periods. Among 
these conditions are chronic nephritis, gout, lead-poisoning, after heavy 
feeding on purin foods, during resolution of pneumonia, in sepsis, etc. 
In the last three of the conditions named there is excessive cellular 
metabolism and consequently temporary overproduction of purin 
bodies. In the first three the higher level of uric acid is probably due to 
some alteration of the renal permeability which maintains a higher 
threshold for the elimination (see below), rather than to any increased 
production of uric acid. 

Gout. — In its typical form gout is a paroxysmal disease marked by 
deposits of urates in the joints and other structures, and by coincident 
or consequent inflammatory disturbances. There are many varieties, 
however, of irregular gout in which the paroxysms may be partly or 
wholly wanting, and in which the disease takes the form of a general 
systemic disorder, or of organic maladies of various sorts. 

Etiology. — Gout is essentially a hereditary diathetic affection, the 
heredity not rarely being polymorphous. By this is meant that in 
certain families gout and other diseases, such as obesity, diabetes, and 
arterial sclerosis, may occur interchangeably. Gout usually develops 
in the later years of life, and among the contributing causes are the 
use of alcohol, overeating, sedentary life, and chronic lead-poisoning. 

Pathological Anatomy. — The conspicuous anatomical lesions are 
those of the joints, and consist of the deposit of urate of sodium in the 
cartilages and connective tissue, and secondary inflammatory changes. 
The latter may cause great distortion and fibrous overgrowth. Similar 
urate deposits may occur in the cartilages of the ear, eye and nose, and 
in the subcutaneous connective tissue or elsewhere. These deposits, 
called the gouty tophi, may subsequently disappear by absorption or by 
discharging through the skin. Cirrhosis in various organs and tissues 
of the body frequently occurs in the course of gout. Among these the 
cirrhotic or gouty kidney is most important. Atheroma, cirrhosis of 



DISORDERS OF NUTRITION AND METABOLISM 



47 



the liver, hypertrophy and fibroid change in the heart, and chronic val- 
vular disease are also frequent. 

Pathogenesis. — For a long time some disorder in the formation and 
excretion of uric acid has been held responsible for the manifestations of 
gout. 

Garrod first demonstrated an excess of uric acid in the blood, and 
recent exact chemical studies have confirmed this observation. There 
are, however, as has been shown, diseases, such as leukemia, nephritis, 
and pneumonia, in which excess of uric acid in the blood occurs without 
any of the results seen in gout. It is possible, of course, that the accu- 
mulation in the blood may be due to different causes in these conditions, 
but it is evident that other factors beside the mere presence of excessive 
uric acid are operative in gout. 

The excretion of uric acid in the urine is found reduced just before an 
acute paroxysm of gout, increases above the normal during the attack, 
and then falls to about the normal. In chronic cases without attacks 
the excretion is about normal. The increased quantity in the blood 
might then be due to increased production or to a reduced transforma- 
tion to simpler metabolic products. Neither of these explanations 
seems justified. At present the more probable reason seems to be a 
change in renal permeability (without any special renal lesion), as a 
result of which the threshold of excretion is raised. The reduction of 
uric acid before attacks has been attributed to the deposition of acid 
urate of soda in the joints and elsewhere, though the amount of uric 
acid in all the deposits falls far short of that which could explain this. 
Possibly changes in diet or intestinal absorption may play a part in this 
reduction. 

The pathogenesis of the urate deposits remains obscure. Ebstein 
first insisted that local necrosis, itself perhaps the result of excess of uric 
acid in the blood, is the direct occasion for the deposits, and some recent 
authorities believe that a primary and essentially gouty local inflam- 
mation invites urate deposits, the uric acid itself having no importance 
in the first condition. Experiments have, however, shown that uric 
acid is capable of causing local inflammatory lesions. Traumatism and 
circulatory conditions may play a part in localizing gouty precipita- 
tions. 

Possibly the conditions in which uric acid is held in solution in the 
blood may differ in gout from those in health and other diseases. 

Studies of the general metabolism in gout show a uniform tendency 
to nitrogen retention, apart from any possible reduction in uric acid ex- 
cretion. There is also a reduction of intestinal absorption, with in- 
creased excretion of indican. 

Diseases of Carbohydrate Metabolism. — The carbohydrates of 
the diet are converted into dextrose or glucose before absorption, this 
conversion being accomplished by salivary and gastro-intestinal en- 
zymes. After absorption into the blood the dextrose is converted into 
glycogen and stored in the liver cells, or, in cases of excess above the 
hepatic capacity of storage, in the muscles. Normally, there is a storage 



48 



A TEXT-BOOK OF PATHOLOGY 



of glycogen sufficient to supply the nutritional needs for as much as five 
days ; in fasting experiments it has been clear that the nutritional needs 
have been supplied by glycogen during the first few days. It has been 
a subject of much investigation and discussion whether or not other 
sources of sugar exist besides the ingested carbohydrates. Recent studies 
have shown beyond doubt that the amino-acids of protein catabolism 
may furnish considerable quantities of sugar by deaminization and sub- 
sequent conversion of the oxyfatty acids into glucose. In severe diabetes 
this may be a noteworthy source of sugar. It is conceivable that the 
glycerole derived from the splitting of fat may also furnish sugar, and 
this derivation seems probable, though it has not been definitely proved. 

The blood maintains a fairly constant sugar content under normal 
conditions — the amount being about 0.080 gm. per 100 c.cm. With 
normal quantities of sugar in the blood, glucose ordinarily fails to 
appear in the urine because a certain threshold of retention prevents 
its excretion through the kidneys. When the blood sugar is reduced the 
glycogen stores of the liver will replace the loss. There is thus main- 
tained a fairly constant level of sugar concentration. When the sugar 
reaches a high level — beyond the storage capacities for glycogen in the 
liver and muscles — the excess is deposited as fat in the areolar tissues. 
Still higher levels of sugar concentration may exceed the. capacity for 
storage as glycogen or fat and the threshold of renal permeability. Glu- 
cosuria then results. 

Ultimately, sugar is oxidized in the muscles and converted into CO2 
and H 2 0. The glycogen stores in the liver are in cases of need con- 
verted into dextrose, delivered to the blood, and finally burned in the 
muscles. The glycogen stores of the muscles are not available for 
maintaining the sugar content of the blood, but are utilized only by 
oxidation in the muscles themselves. 

Hyperglucemia. — Excess of blood sugar — a condition termed "hy- 
perglucemia" — may be a temporary result of ingestion of starches or 
sugar, or a more lasting condition in certain diseases (diabetes, thyroid 
diseases, hypophysis diseases, cancer). Under normal circumstances the 
liver is capable of storing as glycogen any amount of sugar derived 
from mixed or starchy diet. The processes of digestion and absorption 
do not furnish to the- blood amounts of sugar sufficient to overbalance 
the storage capacity of the liver. Pathologically, the liver* may fail 
to store the sugar and the excess in the blood may occasion excretion in 
the urine (hyperglucemia-glucosuria). In normal cases the blood sugar 
after a meal may increase in one or one and one-half hours to 100 or 
125 mg. per cubic centimeter, but the amount quickly falls to its 
former level. 

Alimentary Glucosuria. — When large quantities of sugar (dextrose, 
fructose, or other forms) are ingested the capacity for storage may be 
exceeded and glucose may appear in the urine. Under certain patho- 
logical circumstances (diseases of the liver, alcoholism, thyroid disease) 
the ingestion of relatively small amounts of sugars may be followed by 
glucosuria (glucosuria e saccharo), and even starch ingestion may occasion 



DISORDERS OF NUTRITION AND METABOLISM 



49 



a like result (glueosuria ex amylo). Sometimes the glucosuria in such 
cases may perhaps be due to the fact that the liver is already stored to 
its capacity and cannot accommodate additional deposits of glycogen. 

Glucosuria Due to Excessive Hepatic Glycolysis. — Under certain 
circumstances the liver converts its stored glycogen into glucose so 
rapidly that hyperglucemia and glucosuria result. This seems to be 
the explanation of the glucosuria occasioned by Claude Bernard's 
classical experiment of puncture of the medulla and by certain poisons 
such as chloral, morphin, antipyrin, etc. 

General Scheme of Possible Causes of Glucosuria 

1. Alimentary — excessive ingestion of starches and sugars beyond the 
storage capacity of liver and muscles. 

2. Defective hepatic glycogenesis — incapacity of the liver to trans- 
form and store as glycogen. 

3. Excessive hepatic glycolysis — too rapid conversion of glycogen 
into glucose. 

4. Defective muscular glycogenesis — incapacity of the muscles to 
transform sugar and store as glycogen. 

5. Excessive muscular glycolysis — conversion of muscle glycogen 
into sugar and excretion as such. 

6. Inability of the muscles to oxidize sugar. (See Diabetes.) 

7. Increased renal permeability for sugar. (See Diabetes.) 
Clinical Causes of Glucosuria. — Glucose appears in the urine under 

a variety of conditions, including dietary excesses; various infectious 
diseases; intoxications (morphin, strychnin, chloral, acetanilid, etc.); 
concussion, injury and diseases of the central nervous system; after 
convulsions; in thyroid and hypophysis diseases, and in diabetes melli- 
tus. 

Diabetes mellitus is a disease in which polyuria and glucosuria 
are marked symptoms. It is not improbable that the term includes 
disorders of quite different sorts, but no certain- differentiation of such 
is possible at the present time. A mild and a severe form are distin- 
guished, and these present some striking differences, to which reference 
will be made below. 

Etiology. — Diabetes is frequently a hereditary disease, occurring 
in families in which the same disease or obesity and gout have occurred. 
The Jews seem particularly liable to it. Overeating, sedentary life, 
and gout are causes of some importance, especially of the milder form. 
Sometimes abnormal conditions of the nervous system may be the 
underlying cause. Among these are functional depressions, as in cases 
of excessive grief; traumatic injuries with concussion of the brain; and 
local diseases at the base of the brain in the vicinity of the medulla. 
Disease of the pancreas is the probable cause in many cases, and may 
possibly play a part in all cases, though demonstrable lesions of the 
pancreas are not present in all. Diabetes may occur in the young or 
after middle life, the milder cases more frequently occurring at the latter 
period. 

4 



50 



A TEXT-BOOK OF PATHOLOGY 



Pathogenesis. — In the milder cases of diabetes the same explana- 
tion may be applicable as that given for glucosuria, viz., the liver and 
muscles do not store up the carbohydrates carried to them, and the 
excess of sugar is not burned up in the tissues. Hyperglucemia with 
consequent glucosuria results. In these cases the withdrawal of car- 
bohydrate food or temporary abstinence from all food causes disap- 
pearance of the glucosuria. There is, however, the fundamental differ- 
ence between mere glucosuria and true diabetes that in the former the 
capacity to burn sugar is unimpaired, while in the latter even in mild 
cases this function is more or less disturbed. 

In severe diabetes sugar continues to appear in the urine in spite 
of complete abstinence from starches or sugars. This is explained by 
the conversion of glycogen into sugar and when this supply is exhausted 
by the formation of sugar from the amino-acids of protein catabolism, 
and possibly also by conversion of the glycerol of fat catabolism into 
sugar. In normal individuals, and even in those suffering with mild 
diabetes, any sugar thus liberated is burned in the tissues. Glucosuria 
does not, therefore, occur. Severe and mild diabetes differ only in degree: 
in one case the power to consume sugars is greatly deficient, in the other 
only moderately so. 

The nature of the metabolic disturbances that lead to this inability 
to dispose of carbohydrates is still very obscure. The influence of the 
nervous system is undoubted. Reference may here be made to the occur- 
rence of diabetes after puncture of certain parts of the brain (medulla). 
Very possibly this experiment as well as certain clinical causes of dia- 
betes act by increasing hepatic glycolysis, and in consequence by flooding 
the blood with sugar. 

Older pathological studies showed that diseases of the pancreas are 
frequently associated with diabetes, and recent experimental investiga- 
tions emphasize this relationship. Total extirpation of the pancreas 
in the lower animals causes diabetes. The relationship between the 
pancreas and diabetes has not been certainly established. Formerly 
Lepine and others believed that the pancreas elaborates a "glycolytic 
ferment," absence of which in cases of disease of the pancreas would oc- 
casion accumulation of sugar in the blood and consequent glucosuria. 
More recently it has been found that a cooperation of muscle extracts 
with pancreatic extracts is necessary to the destruction of sugar, from 
which it would appear that normally pancreatic secretions are carried 
to the muscles and activate the process of oxidation of sugar. It 
seems to have been established that the final oxidation of sugar occurs 
in the muscles and not in the liver. The secretion of the pancreas 
involved in this function is doubtless a product of the islands of Langer- 
hans. (See Pancreas.) Other glands of internal secretion seem to 
have some relation to the pancreas and perhaps to the muscles in the 
development of diabetes. It is known that epinephrin when injected 
into the body may occasion glucosuria, and diseases of the hypophysis 
cerebri also occasion glucosuria. The adrenals and the hypophysis may 
act by restraining normal pancreatic function. 



DISORDERS OF NUTRITION AND METABOLISM 



51 



Renal Glucosuria. — Experimentally, glucosuria may be produced 
by injections of phloridzin, a glucoside which is composed of phloretin 
and glucose. Formerly the explanation of the glucosuria resulting from 
injections of phloridzin was as follows: Splitting of the glucoside into 
glucose and phloretin was supposed to occur in the kidneys, the glucose 
being excreted as such, and the phloretin returning to the circulation and 
reuniting with glucose in the liver or elsewhere to form new phloridzin, 
which underwent the same process as that first administered. Careful 
investigations, however, have shown that phloretin itself does not act 
in this manner, and that the cleavage of phloridzin in the kidney, as 
assumed, is improbable. At the present time the more trustworthy 
explanation of phloridzin glucosuria is that it causes some change in 
renal permeability which occasions active excretion of sugar when the 
sugar concentration of the blood is at or even below the normal level. 
It was early recognized that in cases of phloridzin glucosuria the amount 
of sugar in the blood is not above normal, and this fact was one of the 
confusing conditions that required explanation. In the light of present 
knowledge it would seem that the blood tends to maintain its normal 
sugar content by obtaining glucose from the liver and the diet, while 
the lowered renal threshold allows sugar to escape in the urine. The 
process of excretion of the sugar is probably not an entirely passive one, 
to be regarded as a mere overflow when the concentration of the sugar 
in the blood is above the limits of renal retention ; more likely there is an 
active eliminative process in the kidneys that becomes effective when 
the sugar reaches a certain concentration. It is believed by many that 
certain cases of glucosuria in man are due to a similar disorder of renal 
permeability, and in particular the glucosuria associated with gout, 
arteriosclerosis, and chronic nephritis may be explainable on this basis. 
It is impossible at present to make more positive statements. 

The view that diabetes is due to increased formation of sugar has 
been definitely disproved. 

Metabolism in Diabetes. — The essential metabolic disturbance in 
diabetes is the inability of the body to consume and utilize sugar. In 
mild cases this is a moderately developed defect; in severe diabetes it is 
more and more pronounced, though probably never absolute. As a result 
the sugar concentration of the blood is increased and amounts to from 
0.120 to 0.180 gm. per 100 cubic centimeters, with even higher figures 
soon after ingestion of carbohydrates or sugar. The inability to utilize 
sugar causes increased consumption of fat and proteins and leads to 
emaciation. In mild cases and for a time in severe diabetes overfeeding 
with fats and proteins may prevent loss of weight from destruction of 
the fats and proteins of the body, but eventually this protection of the 
tissues fails to be effective. There is always a tendency to excessive 
destruction of proteins and nitrogenous loss, as the diabetic is unable to 
utilize carbohydrates to protect the proteins. The fats also are con- 
sumed to an excessive degree and their oxidation tends to be abnormal, 
as a result of which the ketone acids and acetone are formed in exces- 
sive amounts. (See Acid Intoxication.) Increased elimination of 



52 



A TEXT-BOOK OF PATHOLOGY 



ammonium and other bases (alkalies, calcium, magnesium) are expres- 
sive of the overproduction of acids and their neutralization by the 
bases in question. 

Pathological Anatomy. — Aside from the lesions already referred to 
as in some way related to the causation of the disease, there are found 
pathological changes of various kinds that result from it. The lesions of 
gout (arteriosclerosis and cirrhotic kidneys) may be of the nature of 
mere concomitants, but similar lesions may be direct results of diabetes. 
Renal diseases are of peculiar interest. Late in diabetes albuminuria 
frequently develops and interstitial nephritis may follow. When this 
occurs the glucosuria and other symptoms of diabetes sometimes sub- 
side. Changes in the liver (cirrhosis) have often been found, and have 
been regarded as causative in some cases. A peculiar form of diabetes 
with hepatic disease and general staining (hemochromatosis) of the skin 
and other tissues has been described under the title diabete bronze. Skin 
eruptions (eczema, furuncles, carbuncles) are frequent in certain forms 
of diabetes, and gangrene of the extremities is common. Pneumonia 
and pulmonary tuberculosis are among the frequent developments of 
late stages of the disease. Chronic endocarditis, neuritis, and cataract 
are not uncommon lesions. 

Pentosuria. — Pentose (a sugar containing five carbon atoms) is found normally 
in the nuclei of cells, the total amount in the whole body being estimated as approxi- 
mately 20 gm. Occasionally pentosuria is met with either in combination with 
glucose in diabetes or as an independent condition unattended by symptoms and 
tending to occur in several members of a family. It is certainly not due to the inges- 
tion of pentoses in the diet, and is probably an independent metabolic disorder 
sometimes associated with diabetes, but at other times wholly independent. 

Oxaluria. — This term is, strictly speaking, applicable only to increase of oxalic 
acid in the urine, but is usually employed for cases in which crystals of oxalate 
of lime are found abundant in the urine. The normal maximum of oxalic acid is 20 
mgr. for twenty-four hours. True oxaluria determined by chemical estimation of 
the total excretion of oxalic acid has been found in jaundice and in some cases of 
diabetes. The source of oxalic acid in the urine is still somewhat in doubt. Several 
investigators claim to have found that the older view regarding its presence in 
excess in the urine following certain kinds of vegetable diet is erroneous, and that 
there is no such thing as "alimentary oxaluria." The weight of opinion, however, 
still favors the older view. There is some experimental evidence for the belief 
that intestinal fermentation is an important factor in the formation of oxalic acid. 
While this may be true, there seems little doubt but that the oxidation of uric acid 
accounts for the presence of much of the oxalic acid in the urine, and that nucleins 
and nucleo-albumin are, therefore, important sources of derivation. The authors 
who have argued in favor of a specific disease marked by nervous symptoms and 
oxaluria based their observations on the presence of an excess of oxalate sediment, 
rather than on chemical examinations. Increased sediment occurs in certain in- 
stances of gout in which the oxalates alternate with uric acid or coexist with this. 
In these cases, as in cases of oxalate calculus in the kidney or bladder, the impor- 
tant causative factor is most probably some alteration in the constitution of the 
urine, such as conversion of monosodic phosphate into the disodic phosphate, that 
reduces the solvent power of the urine for oxalate of lime. 

Metabolism of Phosphorus. — Phosphorus exists in the body in the nuclei of 
cells in combination as nucleic acid, in the bones as phosphates, and in the lipoids of 
the nervous system. The phosphorus of food is absorbed as phosphoric acid, which 
combines with sodium, calcium, and magnesium, and from these combinations is 



DISORDERS OF NUTRITION AND METABOLISM 



53 



utilized in the anabolism of phosphatic compounds of the tissues. The excretion of 
phosphorus takes place through the kidneys and intestinal tract. Phosphorus of 
the diet may fail of normal absorption in the presence of excess of calcium, which, 
combining with phosphoric acid, is discharged in the feces. Under ordinary condi- 
tions the phosphorus of the urine, like purin output, is a measure of nucleic metab- 
olism. Excess of phosphorus elimination may be encountered in cases of destruction 
of bone. 

Phosphaturia. — This term should be restricted to increased excretion of phos- 
phoric acid rather than to the presence of increased phosphate sediment in the 
urine. The latter may be due simply to want of acidity of the urine. The daily 
maximum of phosphoric acid with ordinary diet is from 3.5 to 4 gm. The term "phos- 
phaturia" might also be applied to cases in which no absolute excess of phosphoric 
acid is found, but in which this substance is relatively in excess when compared 
with the excretion of nitrogen. The normal proportions are from 17 to 20 parts of 
phsophoric acid for 100 parts of nitrogen. Phosphaturia in the sense just described 
has been found in some cases of inanition. Decided increase in the phosphatic 
excretion, absolute as well as relative, occurs in some cases of diabetes; also in cases 
of tuberculosis and disease of the bones, such as ostitis and osteomyelitis. In 
considering the question of phosphatic excretion in the urine it is important to remem- 
ber that the greatest portion of phosphoric acid is derived from the food, only minor 
quantities coming from the metabolic consumption of tissues. Further, it must 
be remembered that much of the phosphoric acid of metabolism is excreted through 
the bowel. Recent observations show that when there is some intestinal disorder 
preventing excretion of calcium from the intestines there may be excess of phos- 
phoric excretion in the urine in combination with calcium. The term diabetes phos- 
phatides has been used by Teissier for phosphaturia in the sense of increased total 
excretion, and four varieties have been described : (a) cases with polyuria and marked 
nervous symptoms; (b) cases preceding or accompanying pulmonary diseases, espe- 
cially tuberculosis; (c) cases in w T hich phosphaturia alternates with or coexists with 
glycosuria; and (d) cases in which oxaluria, polyuria, and slight albuminuria are 
present and in which there is some relationship with gout. 

The nature of the metabolic disturbances in phosphaturia are obscure. Some- 
times the disorder of metabolism seems to be merely quantitative; in other cases, 
doubtless qualitative. 

FEVER 

Definition. — It is not easy to define this term accurately, though 
we may regard as fever a condition in which the temperature of the 
body is elevated above the normal (98.4° F.; 37° C.) and in which the 
tissue-metabolism is altered in the direction of increased consumption. 
There are cases in which the latter is insignificant or wanting, and there 
are other instances in which the temperature remains normal or sub- 
normal under influences that ordinarily provoke fever. It is doubtful 
whether mere elevation of temperature, such as occurs in experimental 
injury of certain parts of the brain, constitutes fever; but unquestionably 
it would be improper to apply this term to conditions of excessive tissue 
destruction without elevation of temperature. 

Nature. — It is important, first, to consider the regulation of the 
temperature in health. In the normal individual heat is produced in the 
body by constant oxidation and other metabolic activities, and the 
excess is dissipated by radiation from the surface and the heating or 
evaporation of excreta. These processes of heat production and heat 
dissipation are regulated in an orderly manner under the influence of the 
nervous system. Special centers for the production, dissipation, and 



54 



A TEXT-BOOK OF PATHOLOGY 



regulation of heat have been described by the physiologists, though 
their location and method of operation still remain in doubt. What- 
ever the exact mechanism may be, it is quite certain that in some way 
the nervous system exercises a control over production and discharge 
of heat. 

The excessive heat of fever may conceivably be due to excess of 
heat production, to diminution of the dissipation, to both of these con- 
ditions, or to increase of both with greater excess of production. In 
most instances of fever in man it appears that production and dissipa- 
tion are both increased, though the latter is insufficient. At the onset 
heat dissipation may for a time be diminished. The increased produc- 
tion results from increased oxidation and other metabolic processes. 
A study of the respiratory exchange of gases shows that oxygen is con- 
sumed in greater quantity than normally, and the quantity of C0 2 
is correspondingly increased. The excess may amount to as much as 20 
per cent., but in part this increased oxidation is due to the stimulation 
of muscular contractions in rigor, etc. Investigation of the excreta 
shows at the same time evidences of more or less rapid and extensive 
tissue waste. The quantity of nitrogen eliminated is in excess of that 
consumed in the food, and wasting of the tissues results. The albu- 
minous elements suffer particularly in the metabolic wasting, the de- 
crease of fat being more especially dependent on insufficiency of food. 

Etiology. — The causes of fever doubtless vary greatly. Direct 
exposure to heat does not affect the temperature more than a fraction 
of a degree in healthy persons, unless the surrounding temperature 
is very great. Ordinarily the heat-regulating mechanism maintains a 
proper adjustment. Excessive heat may, however, bring on fever, as 
in the case of sunstroke. Here, it has been held that the heat leads to 
direct disturbances of the regulating apparatus in the central nervous 
system; but recent investigations seem to show that there are first 
produced toxic substances which secondarily influence the heat-centers 
of the brain. In another class of cases still more direct disturbance of 
heat regulation seems to occasion fever. Among these cases are the in- 
stances of fever in hysteria and other nervous diseases. 

In the great majority of cases of fever it is quite certain that toxic 
substances are the cause of the febrile disturbances. These substances 
may be of quite different sorts. In the case of infections it is known that 
certain substances contained within the bacteria themselves may cause 
fever, and that products of the growth of the micro-organisms may have 
the same effect. These substances are probably of albuminous nature. 
Other albuminous bodies resulting from normal or disturbed metabo- 
lism, independent of the action of bacteria, such as albumoses, peptone, 
tissue-fibrinogen, etc., may be equally potent; and various ferments, 
such as pepsin, fibrin-ferment, diastase, etc., are known to have the same 
power. These facts explain the multiplicity of causes capable of produc- 
ing fever, as any chemical, mechanical, or bacterial injury of the tissues 
may liberate toxic substances, which in turn act upon the nervous sys- 
tem and occasion the phenomena of fever. 



DISORDERS OF NUTRITION AND METABOLISM 



55 



Pathological Physiology. — Fever is accompanied by or leads to a 
variety of disorders. The appetite is lost, there is excessive thirst, 
emaciation is habitual, and the functions of the various organs are more 
or less disturbed. To a large extent these results are doubtless due to 
the presence of toxic substances in the blood and to other changes in this 
fluid. There is always a tendency to inspissation of the blood, the 
number of corpuscles being augmented (relatively) and the specific 
gravity increasing. This is not, however, invariably the CclSCj clS de- 
struction of the solid matters of the blood may exceed the loss of liquid. 
The alkalinity of the blood is more or less reduced by the production of 
various acids in the increased tissue destruction. A common and possibly 
characteristic metabolic process is the hydration of the albuminous 
tissues with formation of albumoses. There is little accurate knowledge 
of the toxic substances in the blood. The original poisons that caused 
the fever may be toxic for the entire organism, and other poisons may 
be produced by the elevation of temperature and the disturbed metab- 
olism. 

Pathological Anatomy. — Definite morbid changes may occur in the 
various tissues of the body, notably the muscles, heart, liver, and 
kidneys. Among these changes are cloudy swelling, fatty degeneration, 
and coagulation necrosis. It is unlikely that these changes are the direct 
result of the increased temperature. More probably they result from 
the action of toxic substances generated in the course of the fever. 

Conservative Effects of Fever. — While fever occasions many dis- 
turbances and leads to various pathological consequences, it is not im- 
probable that there is a certain measure of usefulness in it. Some 
authors have called attention to the fact that rapid reduction of the 
temperature under the influence of antipyretics is often followed by 
harmful consequences. This does not necessarily prove the usefulness 
of the fever, as the antipyretics are all capable of harm in themselves. 
A more definite proof of the uses of fever is that obtained by subjecting 
infected animals to high temperatures or to febrile conditions, and then 
studying the progress of the infection. Under these circumstances it 
has been found that the course of various infections, such as with the 
Diplococcus pneumonicB, the bacillus of typhoid fever, and other organ- 
isms, is much milder and the consequences less serious than in animals 
not placed under the same conditions. These results agree very well 
with experiments with bacteria outside the animal body. For example, 
it is known that many of the bacteria are influenced unfavorably in their 
growth and virulence by excessive temperatures (104° to 107.6° F.; 
40° to 42° C). Whether in the body the temperature affects the micro- 
organisms directly or indirectly through the production of antitoxic 
substances, or in other ways, remains unsettled. It is not unlikely that 
increased circulation and respiration favor the elimination of the toxins 
that cause the fever. Increased toxicity of the urine has been found, but 
the methods employed are open to criticism. 



CHAPTER III 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 
GENERAL DISTURBANCES 

The circulation of the blood is maintained by the rhythmic con- 
tractions of the auricles and ventricles of the heart, aided by the elas- 
ticity of the arteries; by the compression of the veins by the muscles; 
and by the suction of the inspiratory movements of the chest. 

General disturbances of the circulation result from lessened or 
excessive heart power, from arterial disturbances, or from changes 
in the quantity or character of the blood. Muscular and respiratory 
weakness may be contributing causes. 

Weak Heart. — There are various forms of heart disease that may 
lead to disordered circulation. The muscle itself may be weakened from 
overstrain, the fevers or other diseases, the action of poisons or insuf- 
ficient nourishment, as in the anemias or from narrowing of the coro- 
nary artery. The muscle may be soft and cloudy, fatty, or hardened by 
scierotic changes. There may be no evident muscular disease, but 
merely functional weakness. The valves or orifices of the heart may 
be diseased, and regurgitation or obstruction of the blood-flow results. 
Sometimes blood-clots form within the heart and similarly cause ob- 
struction of the current. Finally, pericardial effusions or adhesions or 
tumors pressing upon the heart may seriously disturb its action. 

The result of the weakened state of the heart must be the accumula- 
tion of blood in the venous system. The place of engorgement depends 
upon the part of the heart specially weakened. If the left ventricle 
fails, the blood backs into the left auricle and the lungs. As long as the 
right heart maintains its power the venous congestion goes no further; 
but when this fails, repletion of the right auricle and of the systemic 
veins ensues. When the right heart is first at fault, general venous con- 
gestion is an earlier manifestation. In all cases the arterial pressure falls 
and the blood-current is slowed, whereas the venous pressure is increased. 

Sudden and complete failure of the heart causes anemia of the 
brain and syncope, which may prove fatal if not instantly relieved. 

Hypostatic Congestion. — In cases of serious weakness of the heart, 
in which it is quite unable to maintain an active circulation, the blood 
tends by the force of gravity to sink to dependent parts. This condi- 
tion is known as hypostatic congestion. It occurs very frequently in 
low fevers and quite commonly just before slow death resulting from 
any cause. Dilatation of the vessels from vasomotor paresis, general 
muscular weakness, and the failure of vigorous inspiratory efforts are 
secondary causes. 

56 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 



57 



The blood accumulates in the skin of the back, especially about 
the buttocks. The skin is of a livid color, but is bloodless over the 
bony points; the tissues tend to become sodden from transudation of 
liquid from the blood-vessels. Sloughing and gangrene (bed-sores) 
may result. Internally, hypostatic congestion affects the lungs par- 
ticularly, and a form of pneumonia may follow. 

Postmortem lividity is allied to hypostatic congestion. After death 
the blood gravitates to the dependent parts and accumulates in the 
veins, as the arteries contract when the heart-action ceases. 

Overaction of the heart is less frequent than weakness. Tem- 
porary overaction occasions increased activity of the circulation and 
elevation of blood-pressure, sometimes sufficient to cause hemorrhage. 
More prolonged overaction due to overwork, to excessive feeding, or to 
nervous stimulation, as in Graves' disease, causes hypertrophy of the 
left ventricle, and later of the whole organ. In consequence the circu- 
lation may be more or less permanently overactive. 

Arterial Disorders. — Both organic and nervous disturbances are 
important. Of the organic disturbances the most frequent is sclerosis of 
the arteries, which offers a constant impediment to the arterial circula- 
tion. Hypertrophy of the heart overcomes the obstacle, but when the 
heart fails venous congestion and dropsy ensue. Sclerosis may also 
affect the veins, but much less commonly. Local diseases of the aorta, 
as congenital narrowing, compression by enlarged glands or tumors, 
aneurysms, and blood-clots may obstruct the flow of blood to the 
arteries, and thereby cause stagnation of the blood in the heart, lungs, 
and venous system. 

Vasomotor disturbances are dependent upon the nervous system. 
Under the influence of certain diseases of the nervous system or of 
poisons (as carbonic acid gas in asphyxia) acting locally on the vessels 
or upon the vasomotor center in the brain, contraction of the smaller 
arterioles occurs; and in consequence the blood-pressure is greatly 
elevated, the heart is impeded, and venous congestion results. On the 
other hand, the arterioles may distend from vasomotor paresis, the 
blood-pressure falls, and unless the heart is active there is a tendency to 
hypostatic congestion. 

Changes in the Blood. — Increase and decrease of the quantity of the 
blood are generally merely passing conditions to which the circulation 
readily adapts itself by dilatation or contraction of the vessels. Sudden 
losses of blood, if large, may be fatal by syncope. Smaller losses are soon 
repaired by absorption of water from the tissues and by regeneration of 
blood. Increase in the quantity of the blood by ingestion of liquids 
never disturbs the circulation greatly. Rapid excretion soon reduces 
the quantity to the normal. 

Changes in the character of the blood may affect its circulation. 
The accumulation of carbonic acid and probably other effete products 
of tissue change impede the flow by exciting vasomotor contraction. 
This is probably brought about by the action of the poisons on the 
terminal nerve-filaments in the blood-vessels or directly on the walls of 



58 



A TEXT-BOOK OF PATHOLOGY 



the vessels. This is the best explanation of the increase of pressure in 
cases of Bright's disease without arteriosclerosis. The poisons in this 
case are quite possibly retained substances which the damaged kidney 
cannot excrete. 

The changes in pressure cited above may be largely due to changes 
in the viscosity of the blood. In general, anything which increases the 
cellular content or molecular concentration increases pressure, while the 
reverse is naturally the case. The chromaffin system, particularly of 
the adrenals, seems to have a stimulating effect upon blood-pressure. 
It is believed by some observers that an overproduction of epinephrin 
is responsible for chronic arterial disease. 



LOCAL ANEMIA 



Local anemia or ischemia is the condition in which a tissue contains 
less than its proper quantity of blood. This may be direct when it results 
from causes obstructing the flow into the arteries, or collateral when it 
is due to withdrawal of blood into hyperemic areas in other parts of the 
body. Of the causes acting directly, pressure is the most frequent. 
There may be general pressure upon an organ or localized area of the 
body, as in the application of elastic band- 
ages; or pressure upon the vessels within the 
tissue itself, as in amyloid disease, the amyloid 
substance compressing the arteries and capil- 
laries, or there may be direct compression of 
an artery by tumors. The circulation in an 
artery may be impeded by sclerosis of the ves- 
sel walls and by emboli or thrombi within the 
vessel. Local anemia of moderate or even 
severe grade may be due to nervous influences 
acting through the vasomotor system, as in the 
earlier manifestations of Raynaud's disease. 
Collateral anemia is well illustrated by the 
anemia of the brain occurring in animals in 
which the splanchnic nerves have been cut, 
with the consequent production of abdominal 
hyperemia. When ischemia is due to obstruc- 
tion of a single vessel the circulation is gener- 
ally soon restored by collateral anastomosis; 
the collateral vessels sometimes reach consider- 
able dimensions (Fig. 1). When an artery which has few anastomoses 
and which soon splits up into capillaries is obstructed the phenomena 
of infarction (see page 66) ensue. 

An anemic area is pale, reduced in size and temperature, and func- 
tionally less active than normal. If the condition persists, fatty de- 
generation and necrosis results. When a severe local anemia is relieved 
it is apt to be followed by hyperemia of the same area, due to exhaustion 
or- degenerative weakness of the vessel walls. 




Fig. 1. — Anastomoses 
three months after ligation 
of the femoral artery of a 
dog (Porta). 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 59 



LOCAL HYPEREMIA 

Local hyperemia is increase in the quantity of blood in a part of the 
.body. This may be due to increase of the flow to that part, or to ob- 
struction of the outflow. The former is called active or arterial hyperemia 
or congestion; the latter, passive or venous hyperemia. 

Active hyperemia occurs in organs during periods of functional 
activity, the increased blood-supply here being due to increased demand 
for nutrition. Pathologically, active hyperemia is due to causes which 
lead to dilatation of the arteries of a certain part. This dilatation may 
be due to influences acting through the vasomotor nervous system or to 
local affections of the vessel walls. The vasomotor nervous system may 
be affected at its center in the medulla or peripherally. The latter is 
seen when the sympathetic, nerves, which contain vasoconstrictor fibers, 
are severed or compressed by tumors, the vessel walls thereby becoming 
paralyzed {neuroparalytic hyperemia). The superficial congestive hy- 
peremia in fevers is probably due to the central vasomotor action of the 
toxic causes of fever. On the other hand, the vasodilator fibers in the 
spinal nerves may be stimulated, as in certain cases of neuritis, with 
a similar result {neurotonic hyperemia). Direct injury to the vessel 
walls by heat, traumatism, inflammation, chemicals, or by the vascular 
fatigue following temporary stoppage of the circulation is a frequent 
cause. 

Active hyperemia is spoken of as collateral when anemia in one part 
leads to overfilling of the vessels of an adjoining or even distant part. 

The hyperemic area is bright red in color, the temperature is ele- 
vated, and there is slight swelling, due to the increase of blood in the 
part and transudation of serum into the tissues. After death the dis- 
tended arteries and capillaries may contract and the part grows paler. 
Arterial hyperemia is one of the phenomena of beginning inflamma- 
tion, and in any case if prolonged may terminate in inflammation. 
Functional activity is increased by moderate congestions. 

Passive hyperemia is due to impediments to the outflow of the 
blood through the veins. This may be brought about by compression 
of veins by tumors, by thickening of their walls, or by thrombi within. 
Little disturbance results from obstruction of a small vein, because of 
the freedom of collateral circulation, provided the heart is active. 
In cases of weak heart-power, however, slight obstructions may de- 
termine local venous hyperemia, or by gravity alone the blood may 
accumulate in dependent parts. The latter constitutes hypostatic con- 
gestion. 

Areas the seat of passive hyperemia are dark red {cyanosis) and 
lowered in temperature. The veins are distended, and very soon the 
watery elements of the blood transude and the part becomes edematous 
and swollen. In severe cases red blood-corpuscles escape by diapedesis. 

This occurs in the small veins and capillaries, but not in the ar- 
teries. In consequence of the increased intravascular pressure the red 
corpuscles are pushed through the wall of the vessel at the angular 



(ill 



A TEXT-BOOK OF PATHOLOGY 



junction of adjacent endothelial cells. At these points the cement sub- 
stance is found in greater abundance than along the borders of the cells, 
and the escape of the corpuscle takes place through the semisolid cement 
substance. 

Later fatty degeneration results from the imperfect nutrition of 
the tissues; or even necrosis and gangrene may occur. In long-con- 
tinued moderate passive hyperemia over- 
growth of connective tissue, due either to 
direct irritation or a replacement process, 
or both, and pigmentation of the tissue 
by broken-down blood-corpuscles is ob- 
served (brown induration). 

Complete stoppage of the circulation 
in a localized area is called stasis (Fig. 2). 
This may be an extreme grade of passive 
hyperemia. The blood-corpuscles accu- 
mulate in the small vessels (arteries, 
capillaries, and veins), and the plasma is 
slowly pressed through the vessel wall or 
onward in the vessel. There results a fill- 
ing of the vessel with a homogeneous red 
material, which is composed of the red 
corpuscles so closely packed as to be in- 
distinguishable. On relief of the stasis 
Fig. 2— stasis of blood in the the corpuscles become free again. Stasis 
vXr" fi dSeIsf Had heart 6 faihire may also be produced by chemical agents 
(modified from Ziegler). which rapidly withdraw the plasma from 

the vessels, leaving the corpuscles unable 
to circulate; or similarly by rapid evaporation of the liquor sanguinis 
from internal structures (as the peritoneum) exposed to the air. 

Passive congestion of any grade and stasis interfere with functional 
activity in two ways: by the reduction of nutrition of the cells and by 
the pressure exercised upon them by the accumulating blood and serum. 
These areas are at first protected against infection because of the excess 
of venous blood, which has a high restraining power upon germs. 

HEMORRHAGE 

By hemorrhage is meant the escape of the several constituents of the 
blood from the blood-vessels. It is said to be arterial, venous, or capil- 
lary, according to the vessel from which the flow of blood takes place, 
and parenchymatous when it comes from all of the vessels. Hemorrhage 
may occur either by diapedesis and extravasation through intact vessels 
(hemorrhage per diapedesin) or by actual rupture of a vessel {hemorrhage 
per rhexin). The former process is seen only in the capillaries and smaller 
veins; the latter occurs mainly in the arteries and veins. 

Emigration and Diapedesis. — Under normal conditions a certain 
number of white corpuscles, by virtue of their ameboid movements, 




DISTURBANCES OF THE CIRCULATION OF THE BLOOD 61 



escape from the capillaries, and become wandering cells which move 
about in the tissues or are carried by the lymph-stream. This process is 
called emigration. There is at the same time some transudation of 
plasma, which, with the leukocytes, enters the lymphatic circulation. 
Under certain abnormal conditions the red corpuscles also pass through 
the vessel wall and collect in the tissues. This is known as diapedesis 
(Fig. 3). It may be studied very readily under the microscope in the 
mesentery of a living frog. It is noticed that the red corpuscles approach 
certain parts of the wall of the capillary or vein and become fixed; then 
a small projection appears outside the vessel, opposite the corpuscle, 
and as this increases the corpuscle within grows smaller, until the whole 
body has gradually passed through. Not rarely several corpuscles pass 




Fig. 3. — Diapedesis of the red blood-eorpuseles through a capillary of a frog's tongue 

(after Thoma). 

through in one mass, as has been particularly noted by Thoma. Out- 
side the vessel the corpuscle at once assumes its ordinary shape. 

Diapedesis was first studied by Strieker and Cohnheim. Arnold, whose investi- 
gations are most important, first believed that the emergence of the red corpuscles 
takes place through orifices or stomata; but later recognized, as is now generally 
believed, that the supposed stomata are merely accumulations of intercellular sub- 
stance in certain places between adjoining endothelial cells or at the junction of 
several cells. The active cause of the extrusion of the red corpuscles is the pressure 
of the blood. It has been thought that chemical changes in the endothelial cells or 
the so-called stomata must precede the diapedesis. 

The leukocytes emigrate from the vessel in exactly the same way 
as the red corpuscles, but mainly by their own ameboid movements. 
At the same time there is a more or less copious overflow of plasma. 

Diapedesis is readily induced by mechanical compression of a 
vein, which elevates the blood-pressure; or it may follow elevation 
of blood-pressure from any other cause. On the other hand, with 
normal pressure increased permeability of the vessel walls may occasion 
diapedesis. Such degenerative conditions of the vessels may be due to 
the action of poisons, to various infectious diseases, to moderate trauma- 



62 



A TEXT-BOOK OF PATHOLOGY 



tism, or to temporary obstruction to the flow of blood into a certain 
area. Perhaps also altered states of the blood may play a part when 
both the vessels and pressure are normal. Hemorrhages by diapedesis 
are generally small and punctate (petechia), but may be quite large, 
as sometimes in the conjunctiva. 

The solution of the endothelia or the intercellular cement substance 
may be caused by many toxins, and seems not to be dependent on any 
one chemical substance. 

Multiple ecchymoses may result from obstruction of capillaries or 
small blood-vessels. Such obstructions occur in the form of hyaline 
thrombi in various infections, as a result of burns or freezing of the skin, 
as well as from exogenous and endogenous poisoning. Fat embolism and 
embolism of parenchymatous cells may bring about the same result. 

Causes of Hemorrhage. — The ordinary form of hemorrhage per 
rhexin may be due to traumatism, to diseases of the vessels, to increase 
of the blood-pressure, and to certain vague nervous influences. 

1. Traumatic hemorrhage may be due to direct laceration of a vessel 
or to contusions which merely weaken the vessel wall and lead to sub- 
sequent rupture. 

2. Diseases of the blood-vessels causing hemorrhage generally 
originate from causes within the vessel, and are due to such conditions 
as poisoning, infections, cachexias, or the anemias. Among the diseases 
of the vessels are fatty degeneration of the intima or media, atheroma, 
and miliary aneurysm. On the other hand, the outer coat may be 
eroded by surrounding disease and hemorrhage ensues (hemorrhage per 
diabrosin). This is seen in phthisic cavities in the lungs. 

3. Increase of blood-pressure may be absolute or relative. The 
former occurs from emotional excitement, from hypertrophy of the 
heart, during paroxysms of whooping-cough, croup, and various con- 
vulsive disorders. In asphyxia there is decided increase of blood- 
pressure both from vasomotor contraction and from the violent muscular 
efforts. Relative increase of pressure occurs when the pressure external 
to the vessel is reduced, as in balloon ascensions, or in the pleura in cases 
in which during violent inspiratory efforts the air cannot enter the lungs, 
as in the fetus attempting to breathe during labor. 

4. Neuropathic Hemorrhage. — The nervous system exercises a 
peculiar influence upon the vessels. In cases of apoplexy, of epilepsy, 
and of section of the spinal cord and in other nervous conditions spon- 
taneous hemorrhages from the nose or stomach, or into the lungs, 
suprarenal bodies, and other organs, are not infrequent. In the same 
group also are to be reckoned the instances of vicarious hemorrhage due 
to suppression of the menses and the remarkable cases of somatiza- 
tion. The last named is a condition in which under nervous exaltation 
or hysteria spontaneous hemorrhages occur from various parts of the 
body, especially from the parts wounded in the Crucifixion. 

5. The Hemorrhagic Diathesis. — Certain persons present an in- 
herited tendency to bleed spontaneously or after very trivial injuries. 
Such persons are known as "bleeders," and the condition as hemophilia. 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 



63 



The exact pathological condition which occasions the hemorrhages is still 
uncertain. Hemophilia is a familial disease manifested by extraordinary 
tendency to bleed either spontaneously or upon trivial injury. The hem- 
orrhage may be external, submembranous, or interstitial. The diathesis 
is transmitted by the females and expressed by the males. The reverse 
has been known to occur. There is a lower coagulability of the blood, 
a prolongation of the clotting time, and probably a lowered tonicity of 
vessel walls. Rudolph and Cole cite two cases in which the clotting 
times were nine and one-half and nineteen minutes. 

A hemorrhagic diathesis may also be developed as a result of 
various diseases, as typhus fever, anthrax, septicemia, or phosphorus- 
poisoning. The same is observed in the severe forms of anemia, like 
progressive pernicious anemia and leukemia. In these cases altered 
blood states and disease of the vessel walls are doubtless the causes at 
work. 

Classification of Hemorrhages. — Hemorrhage may occur on free 
surfaces or into the tissues. In the former case various names are ap- 
plied to designate the locality, such as epistaxis, nosebleed; hemoptysis, 
hemorrhage from the lungs; hematemesis, from the stomach; enteror- 
rhagia, from the bowel; metrorrhagia, uterine hemorrhage between, and 
Menorrhagia, at the menses. 

Hemorrhages into the tissues take their names from the size and 
nature of the lesion. A hemorrhagic infiltration beneath a surface, 
as of the skin or mucous membrane, is called an ecchymosis, which if 
small and well defined is a petechia, but if large and diffuse, a suggillation 
or suffusion. A distinct accumulation of blood, constituting a veritable 
blood-tumor, is known as a hematoma. Infiltrations of a peculiar sort, 
involving localized portions of a tissue or organ, are known as hemor- 
rhagic infarcts (q. v.). 

Results of Hemorrhage. — A very large hemorrhage may cause 
sudden death by cerebral anemia. More frequently the patient remains 
collapsed for a time and then slowly recovers. The hemorrhage ceases 
spontaneously by the diminution in heart action, by clotting of the 
blood at the point of rupture, by retraction of the elastic vessels, and by 
pressure of the surrounding tissues. Blood extravasated in the tissues 
soon coagulates and subsequently undergoes disorganization, the red 
corpuscles breaking down into pigment matter, which may be carried 
away or deposited at the seat of hemorrhage. The fluid elements may 
be completely absorbed, or, stained with coloring-matter, may remain 
as a cyst in which cholesterol plates are usually found. The solution 
of a large blood collection is due to leukocytic enzymes and products of 
tissue cell destruction. A focus of hemorrhage may set up reactive in- 
flammation and lead to encapsulation by new connective tissue. Some- 
times hemorrhagic accumulations become inspissated and undergo calci- 
fication. Blood in the serous sacs does not readily coagulate, but mingles 
with the normal liquid secretion. It may be gradually absorbed or may 
undergo degenerative changes, especially when infected by micro-organ- 
isms. Large hemorrhages cause acute anemia; repeated small extra va- 



64 



A TEXT -BOOK OF PATHOLOGY 



sations may lead to profound secondary anemia. . (These conditions 
will be more fully discussed under Diseases of the Blood.) 

EMBOLISM 

Embolism is the process in which foreign bodies of various kinds 
are carried in the blood and deposited in the smaller arteries or capil- 
laries through which their size does not permit them to pass. The 
bodies deposited are called emboli. 

Sources and Nature of Emboli. — The most common form of em- 
bolism is that in which portions of thrombi situated in the heart, the 
large veins of the extremities or pelvis, or on atheromatous patches in 
the aorta, are swept into the circulation and lodge in the smaller vessels. 
Softening of the original thrombus is generally the immediate cause. 
More rarely portions of a diseased heart-valve or of the intima of the 
heart or arteries, liver or placental cells, or parts of tumors are carried 
in the circulation and deposited as emboli. Embolism of large giant 
cells of the bone-marrow is common. Disorganization of the blood 
may cause embolism of pigment particles, as in malaria, or of small 
hyaline masses, as in burns and certain forms of poisoning. In cases 
of fracture of bones particles of fat may be dislodged from the marrow 
and enter the circulation, while in wounds of the large veins of the 
neck or elsewhere air-embolism is observed. Finally, masses of bacte- 
ria, scolices of echinococcus,. and other parasites are serious forms of 
emboli. 

Dust-embolism. — Small particles of coal, iron, marble, or clay entering the lungs 
in respiration sometimes penetrate the tissues, are largely taken up by phagocytic 
cells, and for the most part are carried to the bronchial lymphatic glands. If the 
latter are surcharged and soften, the dust particles may gain access to the circulation 
through the efferent lymph-channels of the gland or by rupture of the gland into 
neighboring veins. More rarely dust particles may enter the blood-vessels in the 
lungs directly by penetration. After their entrance into the blood they are depos- 
ited in the capillaries and substance of the liver, spleen, and bone-marrow, where they 
may remain permanently, either free or enclosed in fixed cells, or whence they may be 
removed by wandering cells. The final discharge occurs especially from the lungs, 
the tonsils, the lymphatic structures of the intestines, and from the liver in the bile. 

Air-embolism. — Small quantities of air may occasion no serious disturbances; 
but when large quantities enter the veins the right heart is found full of frothy blood 
and the pulmonary arterioles are occluded by small bubbles. Sudden death in these 
cases is not unusual. Some'experiments in dogs seem to cast doubt on the serious- 
ness of air-embolism, but the matter is not yet settled. (See Caisson Disease.) 

Fat-embolism. — Sudden death may occur when a large number of the pulmon- 
ary vessels are obstructed by embolic oil-drops. When the process is less extensive, 
little disturbance arises, as the oil is soon broken up into droplets and passes through 
the pulmonary capillaries, or it may be absorbed in the lungs. 

Seats of Embolism. — The final place of lodgment of an embolus 
depends mainly on its source. Those derived from the general venous 
circulation are usually carried through the right heart to the lungs, 
where they occlude branches of the pulmonary artery. Emboli in the 
portal circulation may lodge in the liver, or pass through the liver to 
the heart and lungs. 



DISTURBANCES OF THE-. CIRCULATION" OF THE BLOOD 



65 



Retrograde Embolism. — Sometimes portions of thrombi, tumor 
masses, other cellular emboli, or micro-organisms may be transported 
in the veins in a direction opposite to the normal blood-current. Thus 
emboli may be carried upward in the inferior vena cava and into the 
hepatic veins and so into the liver; or from any of the larger veins or 
even from the right heart backward toward the peripheral veins. This 
condition, known as retrograde embolism, is observed when some 
pulmonary disease, such as whooping-cough, emphysema, etc., causes 
increased intrathoracic pressure and consequently a positive instead of 
negative pressure in the large intrathoracic veins. There may be an 
actual retrograde current of blood, or the centrifugal transportation of 
the embolus may be more gradually accomplished by repeated im- 
pulses directed toward the periphery, each of which pushes it a little 
further. 

Emboli coming from the left heart or from the aorta are distributed 
in the general arterial circulation. They are most frequently found 
in the spleen, kidneys, and brain. Other organs or the peripheral vessels 
may likewise be affected, but the results of embolism are less marked 
in them and are frequently overlooked. Emboli from the veins may 
reach the general circulation in cases in which the foramen ovale or 
septum ventriculorum is perforated (paradoxical embolism), or by being 
broken up into smaller emboli in the lungs and thus passing through the 
pulmonary capillaries. The latter is not infrequent in cases of fat- 
embolism of the lungs. 

Results of Embolism. — A large embolus may cause sudden death 
by occluding one of the main branches of the pulmonary artery, one of 
the coronary arteries, or a large cerebral vessel. If the vessel is not 
wholly occluded, secondary thrombosis may complete the obstruction 
and death may be slow. In the case of less important vessels merely local 
anemia results. This may be relieved by establishment of collateral 
circulation, or may cause more or less extensive necrosis if not relieved. 
The original embolus and the secondary thrombus may undergo soften- 
ing or organization in the same manner as ordinary thrombi (q. v.). 

The results of occlusion of smaller vessels by emboli depend on 
the nature of the embolus. They are either purely mechanical when the 
embolus is aseptic, or septic when the embolus contains micro-organisms. 
The important mechanical result of small emboli is the pathological con- 
dition called infarction. 

Metastasis. — The process of metastasis of tumors and of infectious 
diseases is closely allied to that of ordinary embolism, and should be 
considered as that form of embolism in which there arises at the point 
of settlement a condition similar to that at its origin. Small particles 
of tumors in the one case, or of infected thrombi or tissue in the other, 
enter the blood-vessels or the lymphatic channels and are carried to 
neighboring or distant parts of the body, where they lodge in capillary 
vessels. In the case of tumor-embolism the embolus may grow and 
occasion a metastatic nodule; in case of infectious processes secondary 
foci of the infectious disease result. 



66 



A TEXT-BOOK OF PATHOLOGY 



INFARCTION 

Infarcts occur in situations in which there are small arteries having 
only capillary or, at most, very slight arterial anastomosis with neigh- 
boring arteries. Such arteries were called end-arteries by Cohnheim. 
They are found especially in the kidney, spleen, lungs, retina, base of 

the brain, and parts of the heart. 
When one of these is occluded by 
an embolus infarction may occur. 

Infarcts are situated in the 
peripheral part of the organ, and 
are harder than the surrounding 
tissue. They are wedge shaped, 
the base being outward toward 
the periphery of the organ. In- 
farcts may sometimes result from 
occlusion of a number of adjoin- 
ing arterioles or capillaries, and 
in this case are irregular in out- 
line. There are two forms of in- 
farction, the red or hemorrhagic, 
and the white or anemic. The 
former are dark red in color, and 
have the appearance of wedge- 
shaped areas of hemorrhage with 
coagulation. Anemic or white 
infarcts present the same general 
features, but are less elevated and 
are yellowish or grayish in color. 
They are frequently surrounded 
Fig. 4.— Old anemic infarct of spleen. by a zone of congestion or hemor- 
rhage (Fig. 4). 

Formation of Infarcts. — The first effect of occlusion of an end-artery 
by an embolus is stoppage of the circulation beyond the embolus. A 
wedge-shaped anemic area results. This may remain anemic and 
undergo coagulation necrosis, with the formation of an anemic or 
white infarct. In other cases, 'however, the vessels of the occluded area, 
after a temporary period of anemia, become overfilled with blood, ex- 
travasation occurs, and a hemorrhagic infarct results. Various theories 
are offered to explain the persistence of anemia in the first case and the 
overfilling with blood in the second. In anemic infarcts the persistent 
anemia in some cases is due to thrombosis in the venules which receive 
the blood from the occluded end-artery and in the anastomotic capil- 
laries. At times rapid swelling of the parenchymatous cells of the 
organ compresses the capillaries and maintains the anemia. Some con- 
tend that white infarcts are frequently formed by rapid absorption and 
removal of the coloring-matter of the blood from hemorrhagic infarcts. 
In the latter the overfilling of the vessels results either from a back 




DISTURBANCES OF THE CIRCULATION OF THE BLOOD 



67 



flow of blood from the veins (Cohnheim) or from free capillary anas- 
tomosis. The latter would be especially apt to occur when the general 
or local blood-pressure was previously elevated, or when the lodgment 
of the embolus caused reflex contraction of the surrounding vessels, and 
thus overflow of blood into the occluded area through the capillary 
anastomoses. The hyperemia thus produced soon leads to extravasation 
of blood, because the vessels of the occluded areas rapidly undergo 
degenerative changes. The continuance of the dark color in the hemor- 
rhagic infarct is due to deposition of iron-bearing pigment derived from 
hemolysis by autolytic or tissue enzymes. Infarcts in the lungs are 
nearly always hemorrhagic; those in the kidneys and especially the 
spleen are frequently anemic. In the brain irregularly shaped areas 
of anemic necrosis (softening) are the usual result. 

Subsequent Changes. — In anemic infarcts coagulation necrosis and 
caseation are the marked degenerative changes. The broken-down 
tissue is gradually absorbed and reactive inflammation and organization 
cause cicatrization. Not infrequently a small amount of calcareous 
matter is deposited, especially in infarcts of the lungs. In hemorrhagic 
infarcts the extravasated blood breaks up into pigment matter and the 
tissues suffer degenerations similar to those seen in anemic infarcts. 
The final result in either case is generally a scar, which is pigmented in 
cases of hemorrhagic infarcts. More rarely infarcts undergo liquefac- 
tion and cyst formation, especially in the brain. The infarct may 
become infected by micro-organisms after its formation and abscess 
may result, as in cases in which the embolus itself was an infectious one. 

Infectious embolism occurs in cases of purulent softening of thrombi, 
in cases of local suppuration or necrosis, in ulcerative endocarditis, and 
the like. The first effect may be the formation of a hemorrhagic or 
anemic infarct; but the micro-organisms soon multiply and invade the 
tissues, causing suppurative or gangrenous processes. Metastatic ab- 
scesses are produced in this manner. Similar results follow when an 
infarct is secondarily infected. This is not infrequent in the lungs, where 
the air-passages furnish a ready path for the entrance of micro-organisms. 

Pulmonary infarcts may be due to embolic occlusion of the blood-vessels, but 
also to obstruction of a bronchiole. Any kind of hemorrhagic extravasation in the 
lungs may assume a wedge shape, because the area infiltrated is the wedge-shaped 
area included in the divisions of a terminal bronchiole. (For details, see the chapter 
on the Lungs.) 

THROMBOSIS 

Thrombosis is the coagulation of blood within the blood-vessels or 
heart during life. At the very beginning of the process the formation 
is not a coagulum in the ordinary sense, but subsequently coagulation 
is the essential feature. After death clots form within the heart and 
vessels, as in blood removed from the body. 

Causes. — The conditions favorable to thrombosis are alterations 
in the blood-current, changes in the vessel walls, and alterations in the 



68 



A TEXT-BOOK OF PATHOLOGY 



blood itself. For the most part two or all of these conditions are present 
in cases of thrombosis. 

Alterations in the Blood-current. — Anything which slows the current, 
such as narrowing of the blood-vessels, weakness of the heart, or pressure 
upon the vessels, favors thrombosis. Complete arrest of the current in a 
part may lead to ordinary clotting, such as occurs postmortem; but with 
careful precautions a vessel may be ligated at two points without the 
occurrence of clotting in the occluded portion — at least for a long time. 
Some change in the blood-vessel wall is generally necessary in addition. 
Some sudden change in blood-pressure or rate of flow, some back pres- 
sure or blood eddy may permit the settling upon the intima of sufficient 
blood-platelets to start a clot. Thrombi due to slowing of the current 
are frequently seen in the heart, the vessels of the lower extremities, 
and in the sinuses of the brain in the course of exhausting fevers or 
other asthenic conditions. They are called marantic thrombi. In many 
of the latter micro-organisms have important etiological relations. 

Changes in the vessel walls play an important part. Atheroma, 
inflammatory or degenerative changes in the vessels of areas of in- 
flammation or necrosis, ligation and other traumatic injuries, and dis- 
eases of the endocardium are all examples of conditions leading to 
thrombosis. In many cases of thrombosis apparently due to slowing 
of the current of blood micro-organisms have been the more important 
factors by causing primary infective lesions of the endothelium. Dila- 
tation of the arteries (aneurysm) or veins (phlebectasia) or of the cavi- 
ties of the heart acts largely by slowing the current of blood or by pro- 
ducing irregular currents. 

Alterations in the Blood. — It is believed by Aschoff that some altera- 
tion in the blood itself is necessary, and that without this, changes in the 
vessel wall are insufficient. These blood alterations may consist of 
clumping of platelets, collections of hemolvzed red blood-cells, and the 
like. 

Experimentally, thrombosis may be induced by injection into the 
circulation of extracts of the thymus gland, the suprarenal bodies, the 
testicles, and other organs. These extracts contain large quantities of 
the fibrin-ferment regarded by Schmidt as an essential factor in coagula- 
tion. Pathologically, it is probable that the tendency to thrombosis in 
typhoid fever, sepsis, and other diseases is due to increase of similar 
fibrin-forming factors in the blood. The name ferment thrombosis is 
applied in these cases. 

The presence of bacteria in the blood in cases of thrombosis and 
within the thrombi themselves indicates a probable relationship of great 
importance. Some bacteria (especially staphylococci) seem particularly 
potent, while others apparently have little effect. The mode of action 
of the bacteria has not been fully established, but hemolytic activity and 
injurious effects on the lining of the blood-vessels may now be con- 
sidered sufficient to explain thrombosis, on the basis of a reduction of 
the anticoagulating power of endothelium. Bacteria seem able to in- 
duce hyperinosis, or an increase in the fibrin-forming elements. 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 



69 



Hemolytic action is also the probable explanation of the frequent 
thrombosis met with in various mineral poisonings and in auto-intoxica- 
tion such as follows freezing or burns. 

According to present-day views, coagulation of the blood is the result of a 
special form of gelatinous precipitation of fibrinogen, a normal constituent of the 
blood-plasma under the influence of fibrin-ferment or thrombin. The latter is prob- 
ably not a true ferment in its mode of action, but seems rather to enter into a 
physical or physicochemical combination with the fibrinogen. Thrombin is a 
derivative of various cells of the body, especially the leukocytes and vascular endo- 
thelia. It occurs in the cells as prothrombin, which requires for its activation or 
conversion into thrombin, calcium salts and probably also certain so-called thrombo- 
plastic substances derived from tissues. In the blood within normal blood-vessels 
coagulation is prevented by the action of antithrombin (Howell). According to 
the views here expressed the process of coagulation may be tabulated as follows : 

Cells — » thromboplastic substance. Thromboplastic substance + calcium -f- 
prothrombin = thrombin. Thrombin + fibrinogen = fibrin. 

Pathological Anatomy. — The appearance and the construction of 
thrombi depend upon the manner of formation. 

When formed in consequence of almost complete stoppage of the 
circulation they are dark-colored, soft, red clots, similar in every way 
to postmortem coagula; and under the microscope show fibrillar fibrin 
enclosing mainly red corpuscles. 

Yellowish or white thrombi are formed slowly from actively cir- 
culating blood and are more consistent. Their composition will be under- 
stood from the mode of formation. In the normal circulation the red 
corpuscles move in a column in the center of the stream, separated from 
the wall of the vessel by a plasmatic zone in which the leukocytes may be 
seen. When the circulation is slowed, plaques approach the vessel wall, 
and tend to adhere in small masses to any point of disease in the endo- 
thelium and also to each other. This has been termed conglutination 
of the blood-plaques. 

In the ordinary thrombus, after primary conglutination of the 
plaques, leukocytes are added, and red corpuscles in great or small 
numbers, according to the manner of formation of the clot, whether 
rapid or slow. White thrombi consist of conglutinated plaques, leuko- 
cytes, and fibrin. They first appear as hyaline, viscid masses, but sub- 
sequently become granular from partial disintegration. If the circula- 
tion is alternately slow and more rapid, distinct layers are seen in the 
thrombus, first dark colored from admixture of red corpuscles, then 
lighter in hue. Such thrombi are called stratified. If the circulation is 
irregular from dilatation of the vessels or from other causes, the light 
and dark areas of the thrombus may be more irregularly disposed. 

The thrombus first formed is the primary thrombus. Subsequently 
it extends by additions (secondary thrombus) in the direction of the 
current of blood as far as the next collateral branch of the vein or 
artery, into which the thrombus frequently extends as a rounded prom- 
inence. In the case of the veins a new thrombus may start from such 
projection (Fig. 5), and eventually the clot may in rare cases extend as 



70 



A TEXT-BOOK OF PATHOLOGY 



far as the heart (Fig. 6). The thrombus may be lateral— that is, when it 
lies against the vessel wall — or obstructive, when the lumen is completely 
obliterated. In the veins small thrombi are frequently formed in the 
valvular pouches in marantic subjects. In the heart thrombi are espe- 
cially common on diseased valves, in the auricular appendages, and in 




Fig. 5. — Thrombus in the femoral vein in a case of phlebitis (from a specimen in the 
Museum of the Philadelphia Hospital). 

the intertrabecular spaces. They frequently appear as polypoid masses, 
and may be attached by slender pedicles. A curious form, called ball 
thrombi, is seen in the auricles. These are rounded clots wholly or almost 
wholly separated from the wall, and may occasion serious obstruction 




Fig. 6. — Cystic thrombi of heart chamber. 



at the orifices of the heart. The internal softening is probably due to 
leukocytic enzymes acting in the center, protected there from the anti- 
enzyme of the blood. 

Effects. — Frequently the collateral circulation is so quickly estab- 
lished that no untoward results are seen. When a large vein is ob- 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 



71 



structed, venous congestion and dropsy may follow; obstruction of an 
artery causes local anemia, and subsequently, if the collateral cir- 
culation is not established, degenerations or necrosis. Thrombotic 
obstruction of small arteries may cause hemorrhagic infarction. Em- 
bolism and, if the thrombus is infected, general pyemia may result from 
softening of the thrombus. 

Subsequent Changes. — After their formation all thrombi contract. 
In this way the red forms may become light colored by extrusion of the 
red corpuscles, or by hemolysis if bacteria or toxins are responsible for the 
thrombosis. In small vessels red thrombi often become light, colored 
by removal of hemoglobin and a species of hyalin transformation. 
These may have the appearances of white thrombi and are only dis- 
tinguished by careful examination. 

After the thrombus has contracted it may undergo various de- 
generative changes. Frequently the white corpuscles, plaques, and 




fibrin are broken down into an emulsion by liquefaction necrosis and 
fatty degeneration, and the red corpuscles converted into granular pig- 
mented masses. These softened portions are swept into the circulation 
and occasion embolism. Frequently this form of simple softening occurs 
in the center of large thrombi and gives rise to cyst-like formations 

A more serious form of softening occurs when the thrombus is in- 
fected by micro-organisms. In this case true purulent softening takes 
place, and the wall of the blood-vessel shares largely in the suppurative 
processes. This form occurs especially in the thrombi blocking blood- 
vessels of suppurating or necrotic tissues. General pyemia and infec- 
tious embolism result. 

A more favorable termination of a thrombus is calcification. This 



72 



A TEXT-BOOK OF PATHOLOGY 



is most frequent in the clots in dilated veins, the calcareous thrombi 
being known as phleboliths. Arterioliths and cardiolitlis are rarely met 
with. 

Organization of the thrombus may result from the irritation it 
occasions. New blood-vessels and proliferating connective-tissue cells 
spring from the vasa vasorum and lining membrane of the blood-vessel 
as well as from endothelial cells covering the thrombus, and penetrate 
the thrombus (Fig. 8). From these organization proceeds as elsewhere, 
and as it advances the thrombus itself is absorbed. Finally, the clot is 
fully replaced by connective tissue enclosing a small amount of blood- 
pigment or calcified remains of the thrombus. The blood-vessel may 
be converted into a solid fibrous cord, or may be distorted and narrowed 
by bands of connective tissue in the interior. Sometimes after partial 
vascularization of a thrombus small vessels running parallel with the 
lumen of the obstructed vessel become dilated and thus partly reestablish 




Fig. 9. — Canalization of a thrombus (Karg and Schmorl). 

the channel. This is termed canalization of the thrombus (Fig. 9). 
In other cases canalization may begin as a process of simple softening. 

The clotting of blood within body cavities, in extravasations, or upon 
wounds is favored by the presence of tissue coagulins and bacteria in 
addition to the leukocytes and platelets. Hyaline thrombi seen in 
small vessels and free in organs are due to an agglutination of erythro- 
cytes or platelets by bacterial or other toxins. They are probably free 
of fibrin, although staining like it. 

EDEMA 

Definition. — The term "edema" is applied to a condition in which 
the liquid within the tissues is increased in quantity. 

Etiology. — It is primarily necessary to understand the methods by 
which the liquids normally present in the tissues escape from the blood- 
vessels, their original source. 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 73 

Several processes are concerned in this escape of fluid. In the first 
place, the pressure of the blood serves to cause a certain amount of direct 
filtration, just as liquid enclosed in tubes of permeable animal membrane 
escapes when the pressure outside is less than within. In this process of 
direct filtration the state of the tissues themselves plays a part. If the 
normal elasticity of the tissues and degree of pressure of the liquid in the 
interstitial spaces are lowered, liquid escapes through the capillary walls 
to equalize the pressure. A second process at work is that known as 
diffusion or osmosis. In this there is an exchange between the blood and 
the tissue liquids, certain substances being taken into the blood in ex- 
change for water and other constituents of the blood-plasma. The liquid 
thus discharged from the blood-vessels enters into the metabolic activity 
of the tissues to a greater or less degree, is somewhat altered in character, 
and the surplus is carried off in the lymphatic capillaries as lymph. Cer- 
tain physiologists (Heidenhain el al.) believe that there is a further and 
very important factor of a vital sort. This is described as an active 
secretory function of the endothelial cells of the capillaries and lymphatic 
spaces; so that, according to this view, lymph formation is in a measure 
at least a direct secretion. This view, though not generally accepted, is 
supported by many facts. Meltzer suggests that endothelium acts as a 
carrier of lymph and solid particles from the blood to the tissues. 

Briefly, then, lymph formation may be described as the escape of 
water and other substances through a more or less permeable membrane, 
the capillary walls, in consequence of direct filtration, osmosis, and prob- 
ably secretion. The quantity present in the tissues depends upon the 
quantity escaping from the blood-vessels and the amount carried away 
by the lymphatic circulation. 

The causes of increased accumulation of liquid in the tissues may 
then be readily determined. Among these are: (a) increase of blood- 
pressure, or (b) decrease of tissue elasticity and pressure; (c) alterations 
of the blood rendering it more diffusible, or (d) of the liquids in the 
tissues increasing the osmotic power of these; (e) increased permeability 
of the walls of the blood-vessels; (/) obstruction to the flow in the 
lymphatic vessels. These causes will be considered separately with 
reference to certain well-known clinical types of edema. 

(a) Increased blood-pressure always occasions increased escape 
of liquid from the vessels (transudation) and thus increased formation 
of lymph. In active hyperemia with excess of pressure the amount of 
liquid rarely becomes so great that the lymphatic vessels cannot carry it 
off, and edema does not, therefore, occur. In passive congestions, how- 
ever, as in heart disease, pressure upon veins, etc., the escape of liquid 
becomes more rapid and copious, and the lymphatic circulation is insuf- 
ficient. Edema or dropsy results. In this process of direct filtration the 
transudate consists mainly of the water and saline constituents of the 
plasma and to a relatively small degree of the albuminous constituents. 

(b) Decreased tissue elasticity and pressure are rarely factors of 
prime importance, though they may be contributing causes in many 
cases. In one class of cases termed "oedema ex vacuo" they are the 



74 



A TEXT-BOOK OF PATHOLOGY 



principal causes. In these cases liquid escapes from the blood-vessels 
to fill a space left vacant by disease or atrophy of tissue elements. 
This is frequently seen in the subarachnoid spaces of the brain and in 
other parts of the central nervous system. 

(c) Alterations of the blood, though theoretically very important as 
direct causes, probably act indirectly. It has been found by experi- 
ment that artificial hydremia, even though combined with considerable 
increase of the bulk of blood, does not cause edema unless by some 
means the walls of the blood-vessels have been injured. It is probable, 
therefore, that the edema of anemic and marantic persons is similarly 
due to increased permeability of the vessels. This in itself might occa- 
sion edema, though the degree is probably greater as a consequence of 
the anemic state of the blood. The vascular disease itself is probably 
in some way (perhaps by the action of circulating toxic substances) 
brought about by the condition of the blood. 

(d) Increased permeability of the capillary walls is of great im- 
portance and probably plays a part in every case of edema. Experi- 
mentally it is easy to prove that this factor alone may cause pathological 
transudation. Applications of heat to a part or the introduction of 
poisons capable of causing disease of the walls of the blood-vessels may 
thus occasion edema. Clinically this factor is of importance in the 
edema of Bright's disease. Formerly the dropsies of renal disease 
were attributed to hydremia, but the experiments cited above show this 
factor to be insufficient. On the other hand, changes of the vascular 
system are known to occur in Bright's disease, and particularly in cases 
usually attended with marked edema (glomerulonephritis). Changes 
in the blood may, of course, contribute, as may also stasis due to cardiac 
weakness. 

Disease of the capillary walls is also an important cause of edema 
in and about areas of inflammation (inflammatory edema). In these 
cases the toxic causes and products of inflammation doubtless attack 
the walls of the vessels and render them more porous. Such edema may 
occur only in the vicinity of an inflamed area, or may be widespread. 
Thus in some cases edema of the lungs and other internal organs may be 
occasioned by bacterial toxins derived from a distant focus of infection. 

Cases of hereditary edema have been described. These may owe 
their origin to a congenital excess of vascular permeability. 

Finally, there are cases of edema in which the nervous system seems 
to exercise an influence. Among these are the dropsies attending cases 
of neuritis, neuralgia, or organic diseases of the cord. In these instances 
changes in the blood-vessels and perhaps in the tissue elasticity may be 
important causes. An interesting form of this sort is that known as 
angioneurotic edema, in which local edema of various forms (often as 
giant urticaria) makes its appearance under the influence of nervous 
irritations. 

(e) Obstruction of the lymphatic circulation does not ordinarily 
occasion edema because the collateral circulation is sufficient to carry 
away the lymph. When, however, a larger trunk, especially the thoracic 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 75 

duct, or numerous smaller lymphatics are obstructed edema may result. 
This is observed in the chylous ascites due to obstructions of the thoracic 
duct and in the edema of elephantiasis. 

(/) Alterations of the liquids of the tissues may, conceivably, occa- 
sion increased diffusion of liquid, but practically little is known of the 
operation of this element. 

While the escape of fluid from vessels to tissues may be explained 
under the preceding headings, other factors must account for its re- 
maining outside lymph- and blood-vessels. This has been explained 
by the statement that dropsical tissues and fluids contain an excess of 
sodium chlorid. This is not always the case. Fischer claims that in 
parts subject to edema there is increase in acids, in the presence of 
which colloids are altered so that they take up and hold more water. 
The acids accumulate as a result of overproduction through improper 
oxidation or because of abnormal retention. 

Pathological Anatomy. — Edema may take various forms, according 
to its situation. In some cases it is localized, affecting a limited part of 
the body, as a single organ or member. In other cases it is widespread 
in the subcutaneous tissues and skin, when the term "anasarca" is ap- 
plied. It may occur in the serous cavities in the form of serous transu- 
dates (hydrothorax, ascites, hydropericardium, etc.). 

The liquid itself varies in character according to the cause. In the 
pure transudates due to increased filtration the liquid is watery, low 
in specific gravity (below 1016), and comparatively poor in blood- 
corpuscles and albuminous constituents. In cases in which disease of 
the vessel walls has played a large part in the causation, especially in 
the inflammatory edemas, the liquid is more dense and contains more 
corpuscles and albuminous bodies. 

The transudate first occupies the lymph-spaces or interstices of the 
tissues, causing a more or less uniform swelling and bogginess. The 
tissue pits on pressure, and on section more or less abundant liquid 
exudes. The solid organs (kidneys, liver) are lighter in color, less dense, 
and more moist on section than normal; but the appearances of edema 
are here less characteristic than in the subcutaneous or submucous 
tissues, or in the softer organs like the lungs and brain. 

Microscopically, the tissue elements are seen to be pushed apart 
by the transudate, and in some cases the cells themselves may be dis- 
eased. (See Dropsical Infiltration.) 

Results of Edema. — The function of edematous parts is necessarily 
impaired. Sometimes serious consequences ensue, as in the case of 
edema of the epiglottis, the lungs, or the brain. Secondary changes 
may occur in parts the seat of continued edema. Among these are 
various degenerations of the cells and a productive change in the con- 
nective tissues. The latter is well illustrated in the sclerotic change in 
the subcutaneous tissues of long-standing dropsy, elephantiasis, etc. 



CHAPTER IV 



RETROGRESSIVE PROCESSES 
ATROPHY 

Definition. — Atrophy is a condition in which a tissue or organ under- 
goes a more or less uniform diminution without definite disease of its 
constituent parts. It is extremely difficult to draw a sharp line between 
atrophy and degeneration. Frequently one of these conditions merges 
into the other. 

Hypoplasia. — This term is applied to a condition in which certain organs or 
tissues fail of their normal development. Thus the heart and blood-vessels and the 
internal genitalia have been found incompletely developed in some cases of chlorosis; 
and similar conditions have been found in other diseases or apart from manifest 
disease. It is difficult to determine in some cases whether the lack of development is 
purely the result of deficiency in the developmental processes or the result of congen- 
ital disease. Thus, in the state called infantilism, in which the body as a whole re- 
mains undeveloped, there is sometimes a relationship with cretinism or other dis- 
eases of glands of internal secretion, and primary disordered action or deficiency of 
the thyroid gland, hypophysis, etc., is the underlying cause. Occasionally an organ 
or part of the body is entirely wanting. To this condition the name aplasia is 
given. 

Etiology. — The causes of atrophy may be varied. It occurs as a 
result of want of functional demand, as in the atrophies affecting palsied 
limbs; and sometimes as a result of disturbances of the trophic nervous 
system, as in diseases of the anterior horns of the spinal gray matter. 
In the latter instances lack of use is a contributing cause. In the invo- 
lution processes of old age there is more or less general atrophy, which 
might be designated as physiological. Similar normal or physiological 
atrophy occurs in certain organs before the general manifestations of 
old age. Thus, the atrophy of the thymus gland in early childhood and 
of the genital organs at the menopause are instances of cessation of 
function, and consequent or concomitant atrophy of physiological char- 
acter. Atrophy may be more definitely pathological and the result of 
distinct causes, such as want of local or general nourishment by occlu- 
sion of the vessels, pressure, etc. In these cases the process may be 
purely atrophic, or there may be distinct degenerative disease of the 
cells with diminution of bulk. 

Pathological Anatomy. — Atrophy may be simple or numerical. In 
the former kind, to which the term "true atrophy" might also be applied, 
the individual cells decrease in size without manifest disease; in the latter 
the cells are reduced in number, and are usually first altered by some 
form of degenerative disease, so that the process is not, strictly speaking, 

76 



RETROGRESSIVE PROCESSES 



77 



true atrophy. The parenchyma of organs suffers first and most char- 
acteristically, the connective tissues remaining unaffected or even 
undergoing hyperplasia. In true atrophy the cells may present no 
definite alteration, excepting perhaps slightly increased pigmentation. 
This is sometimes due to the fact that the normal pigment does 
not suffer reduction as do the other constituents of the cell, but in 
other cases there is actual deposition of pigment (hematogenous). 
Cases of the latter kind are designated as brown atrophy (Fig. 10). This 
is seen most strikingly in the heart muscle in advanced old age or in per- 
sons dead of some chronic cachectic disease. In 
some of the conditions generally described as 
atrophy the cells show degenerations of various 
forms, such as cloudy swelling, coagulation ne- 
crosis, fatty degeneration with vacuolization, and 
other gross alterations of structure. 

Secondary degenerative changes may occur in 
the connective tissues after the parenchyma cells 
have become atrophic. Thus, after the physi- 
ological atrophy of the thymus gland has oc- 
curred the connective tissues of the gland and 
of the surrounding parts become converted into 
fatty tissue. In other cases myxomatous change may be observed. Such 
a fatty or myxomatous change may give rise to pseudohypertrophy. 

Organs which have undergone atrophy are often quite irregular on 
the surface from unequal involvement of the different constituents. 
The consistency may be little changed or may be greatly reduced, par- 
ticularly when some form of cellular degeneration is present. On the 
other hand, the organ may be hard and tough from secondary hyper- 
plasia of the connective tissue. The capsule is generally wrinkled from 
the shrinkage of its contents, and secondary thickening is not unusual, 
especially in the heart and spleen. The color of the organ, like that of 
the individual cells, often becomes darker than normal, and may be 
decidedly changed in brown atrophy. 

In cases of pressure-atrophy various distortions of the affected 
organ may be observed. These are particularly marked in the livers of 
women who have laced excessively. The right lobe of the organ often 
presents a deep groove or furrow corresponding with the lower border 
of the ribs, and each of the ribs with which the organ comes in contact 
may cause a depression. . 

Pathological Physiology. — The function of an atrophic organ is 
necessarily impaired. In the atrophies of old age this may be of little 
consequence, as the functional demand grows less and less. In premature 
atrophies general as well as local disturbances may occur. These dis- 
turbances vary with the varying functions of the organs, and will be 
separately discussed. 




Fig. 10. — Brown atrophy 
of the heart muscle. 



78 



A TEXT-BOOK OF PATHOLOGY 



The So-called Infiltrations and Degenerations 

There are certain pathological processes of a retrogressive character 
to which the names "infiltration" and "degeneration" have been given. 
Data are growing to show that several of these may be but stages of cell 
necrosis, and that a sharp distinction is not possible between infiltration 
and degeneration. In order- not to confuse the reader the subjects 
will be taken up under their customary names and an attempt will be 
made to show their relationships. 

CLOUDY SWELLING 

Definition. — Cloudy swelling, also termed "albuminous infiltra- 
tion" and "parenchymatous degeneration," may be defined as an 
edema of the cellular protoplasm, with granular alteration in the pro- 
toplasmic protein and the production of opacity. 

Etiology. — Cloudy swelling is an almost universal accompaniment 
of inflammations. Circulatory disturbances (anemia) were formerly 
supposed to be important, but are now considered to be of little sig- 
nificance. Fever per se can produce cloudy swelling, probably not so 
much the result of the simple degree of heat as of metabolic disturbances 
induced thereby. The most frequent cause of cloudy swelling is in- 
toxication, either by bacterial toxins, as in the various infectious con- 
ditions, or by innumerable organic and inorganic substances. Cloudy 
swelling is also caused by nutritional disturbances; starvation of an 
organ will produce it, as the first stage of atrophy; and, on the contrary, 
the cells may in other cases be so overloaded with nutritional sub- 
stances as to become temporarily transformed into this condition, as 
in the glandular epithelium of the liver during active digestion. It is 
further known that excessive cellular activity may result in a cloudi- 
ness of the protoplasm, as in the kidney and in glands excited by nervous 
stimulation. These latter processes should be viewed as normal phe- 
nomena analogous to the physiological fatty degenerations. 

Pathological Anatomy. — The swollen cells present a fine opacity 
which under high powers is seen to be due to the presence of diffuse refrac- 
tile granules (Fig. 11). The normal protoplasmic granulations (Altmann's 
granules) may partly or wholly disappear; in muscle-fibers the stria- 
tions are obscured or obliterated. Vacuolation may be seen in the late 
stages. The cell wall becomes indistinct, so that the cells appear to have 
coalesced. The nuclei may be little altered, but are commonly obscured 
by the degeneration. The nuclei are somewhat more deeply stained 
at first, but shortly undergo some chromatolysis, becoming indistinct 
when their sharpness is destroyed by both the smaller cytoplasm and 
their own degeneration. Generally the chromatin becomes diffusely 
stained; it may elect the acid stains or may refuse all staining. In 
late stages the entire cell may lose its normal reactions to staining 
reagents. The distinctive granules are not soluble in alcohol or ether, 
but are dissolved by acetic acid and alkalies. Cloudy swelling may 
be the forerunner of, or at least go over into, fatty degeneration. 



RETROGRESSIVE PROCESSES 



79 



The large glandular organs, the liver and kidneys, illustrate the 
condition exquisitely. The entire organ is symmetrically swollen; the 
general consistency perhaps a little decreased. On section, the surface 
may be found a little moist and the parenchyma protrudes. The tissue 
presents an opaque pallor, suggesting the appearance of boiled flesh. 

Seats. — The glandular epithelia (liver and kidney) and the muscle- 
fibers are the striking seats of this degeneration. 

Pathological Physiology. — The opacity seems to be due to a coagu- 
lation or precipitation of a part or all of the protoplasmic protein. Some 
systematic writers have attempted to divide it into two groups: albu- 
minous infiltration, in which the material has been deposited in the 
cell and then been precipitated; and albuminous degeneration, in which 
the inherent cellular protein has been precipitated. It is doubtful 
whether this division is justified. The chemical relations are entirely 
obscure. It is as yet incomprehensible how bacterial toxins, them- 

K \ •*■ ' & A ,y r< -V 




Fig. 11. — Cloudy swelling and necrosis of the epithelial cells of the renal tubules, due to 
sublimate-poisoning (Karg and Schmorl). 

selves apparently proteins, can precipitate other and higher proteins. 
In the case of inorganic poisoning (metallic salts, acids) the process 
is more readily understood. The swelling of the cell is probably a simple 
edema, due, it may be inferred, to disturbed osmotic relations. This 
has been termed "granular disintegration," and maybe considered as a 
stage midway between cloudy swelling and dropsical degeneration (q. v.). 

Bell has lately shown that fatty and dropsical conditions of the 
organs give the gross appearance of cloudy swelling, and that all such 
degenerations need not be of the same microscopical appearance. He 
thus believes that the gross diagnosis "cloudy swelling" covers several 
states, and even the minute picture does not indicate an entity. 

The function of organs is more or less disturbed by this form of 
degeneration. Complete recovery is easy and frequent. If, however, 
the causes persist, the cells pass into other degenerations, usually fatty 
metamorphosis. 



80 



A TEXT-BOOK OF PATHOLOGY 



FATTY INFILTRATION 

Definition. — Fatty infiltration is the deposition of fats derived 
from the circulation in cells and tissues which normally contain none, 
or the deposition of an excess of fats in cells and tissues in which it nor- 
mally occurs. 

Etiology. — Fatty infiltration may be physiological or pathological. 
In conditions of general obesity the regular consumption of excessive 
quantities of nourishment may lead to the most marked degrees of fatty 
infiltration; an inherited predisposition and lack of exercise act as 
contributing causes. In rare instances it seems possible that with the 
normal physiological diet persons of exceptional digestive power and 
living under conditions which restrict combustion may become affected 
with pathological fatty infiltration. The condition may occur during 
pregnancy, and is frequent at the menopause. In a large class of cases 
an abnormal diet, or the presence in the diet of substances which aid in 



5 




Fig. 12. — Fatty infiltration of the liver. 



the formation of fats, such as alcohol, are responsible for the condition. 
It is doubtful whether poisons produce general fatty infiltration; they 
frequently, however, indirectly produce local or visceral infiltrations. 
Arsenic and antimony are examples. In cachexias certain organs may 
become loaded with fats, as is sometimes seen in the liver in phthisis. In 
carcinoma the cells of the neoplasm may become infiltrated with fats. 
In organic diseases of the nervous system accompanied by extensive dis- 
integration of myelin, in bone diseases, and even following fractures 
of or operations on bones, the liberated fats are taken up by the circula- 
tion and deposited in susceptible localities. There is a rare form prob- 
ably entirely of senile origin, and also a type which appears at puberty. 
Of general diseases that may cause general fatty infiltration, chlorosis 
and diabetes may be mentioned. Fats may be deposited locally as 
substitution tissue, as in the capsule about sclerosed kidneys, in the 
place of atrophied muscular fibers, in the bones, and about areas of 



RETROGRESSIVE PROCESSES 



81 



local disease. The protective areas of fibrous tissue which wall off 
pathological processes of various kinds may become extensively infil- 
trated. 

Pathological Anatomy. — The fat may be diffuse, in localized areas, 
or in streaks along the planes of fibrous tissue. The appearances naturally 
vary with the tissue affected. The connective tissue rather than the 
parenchyma usually displays the disease. The microscopical picture in 
connective tissues is precisely the same as that of normal adipose tissue. 
The deposits in connective tissue are most prominent in various fasciae 
and along the fibrous strands, under the endothelial membranes, about 
the lymph-channels, between the muscular fibrilla>, and to a marked 
extent just beneath the true skin. In the kidney the collections are be- 
tween the tubules; in the liver, in the fibrous trabecular, but especially 
in the hepatic cells; in the heart, underneath the serosa and between the 
bundles of fibers. Within the parenchyma cells, and this is most marked 
in glandular epithelial cells, the fat is seen as distinct drops within the 
cell wall. The fat-drops are always of considerable size, and soon run 
together, forming one drop, which pushes the protoplasm and nucleus 
against the cell wall, giving the so-called seal-ring appearance. The 
nuclei, though flattened, are usually normally distinct, show a nucleolus, 
and stain well; the cell protoplasm is clear and presents its normal 
granules; the cell wall is intact, though often bulging to accommodate 
the excess of contents. In rare, prolonged, and extreme instances the 
bulk of the fat may be such as to interfere with the functions and 
nutrition of the cells, whose nuclei and protoplasm will then show 
pathological alterations. Crystalline formations, as of margarin and 
cholesterin, and tiny balls of lecithin may be present, but are more 
often seen in fatty degenerations. The fat may be stained with osmic 
acid or sudan III. 

Seats. — The favorite seats of fatty infiltration are the subcutaneous 
and subserous tissues, the mesenteries and omentum, along the fascia?, 
between the muscles, about the kidneys, and in the liver and heart. 
The lungs and central nervous organs are rarely and only slightly 
affected. 

Pathological Physiology. — The above description is intended to 
define this condition rigidly as an infiltration of fat into otherwise normal 
cells or tissues, distinct from any possible formation of fat in them. 
Infiltration arises whenever there is an abnormal quantity of fat in 
the circulation; the causes of this were pointed out in the etiology. 
Infiltration into imperfect or diseased cells may, however, occur with 
only normal quantities of circulating fat. All cells and tissues are not 
of the same degree of susceptibility; when, therefore, isolated areas occur 
in unusual localities a pre-existing disease should be suspected. 

The assumption of fat and its retention in the form of globules must 
be referred to an inadequacy of the oxidative powers of the cell. This 
same is true for fatty degeneration, but here we may have added a 
destruction of the natural fat combination in the cell. Here also the 
absorbed fat remains in small globules or granules. 

6 



82 



A TEXT-BOOK OF PATHOLOGY 



Unless very extreme, fatty infiltration does not seriously embarrass 
the functions nor threaten the existence of tissues, and complete recov- 
ery and restitution are the rule. It may, however, cause mechanical em- 
barrassment or may lead to secondary degenerations, which, particularly 
in the heart, may be of serious consequence to the organ. 

FATTY DEGENERATION 

Definition. — This was formerly defined as a metamorphosis, the con- 
version of the cellular protoplasm into fat. The classical physiological 
illustration is the fat production in the secretion of milk. Here the 
nature of this process has not, however, been determined. The major- 
ity of the secreting cells neither die nor show pathological alterations ; 
while in the case of such as are cast off, as colostrum cells, it has not 
been shown that their fat was not an infiltration. 

Etiology. — Fatty degenerations frequently follow upon cloudy 
swelling, and the causes detailed for the one apply also to the other. 
Of all agents, poisons are the most important. These may be metallic, 
as mercury, arsenic, lead, phosphorus — indeed, most of the metals. 
Compounds which directly bind the hemoglobin or reduce it, or break up 
the red corpuscles, likewise produce it; such are carbonic oxid, chlor- 
ates, pyrogallic acid, some coal-tar compounds, etc. Certain poisons, 
like chloroform, ether, iodoform, and the acids, seem to act directly on 
the cell nutrition. In the case of most of these substances it seems to 
have been shown in more or less accurate chemical studies that the 
poison acts by disturbance of the cellular metabolism. The toxins 
of bacteria are causes of importance, but their mode of action is not 
clear, and the analogy with the metallic poisons which naturally sug- 
gests itself has not been made out. In anemias and cachexias fatty 
degeneration is common; it is rare in uncomplicated chlorosis. The 
degeneration in these cases was formerly regarded as due to suboxida- 
tion. Since, however, it has been shown that no suboxidation occurs 
in such chronic anemias, the degeneration may best be classed as toxic. 
It seems possible, however, that extreme hemorrhage can produce 
fatty degeneration by suboxidation. Metabolic diseases can also pro- 
duce it, as is sometimes seen in diabetes. Fever can produce it, but the 
temperature must be high and prolonged. 

Local fatty degenerations may be caused by local disturbances in 
nutrition, if not too sudden. This is seen in cases of congestion, throm- 
bosis, embolism, atheroma, in tumors, and in tuberculous and syph- 
ilitic deposits. The fatty changes of senility are probably of like origin. 
In the involution of tissues, as in the thymus, corpus luteum, uterus, etc., 
fatty degenerations are common. Trophic disturbances produce the 
degeneration, as is seen in the voluntary muscles. In many pathological 
processes, as in caseation, liquefaction necrosis, and the resolution of 
pneumonia, this metamorphosis plays an important role. In rare 
instances, as mentioned, fatty infiltration may pass into fatty de- 
generation. 



RETROGRESSIVE PROCESSES 



83 



Pathological Anatomy. — Organs the subject of marked fatty de- 
generation are often somewhat increased in size; to this, however, there 
are many exceptions : a notable one is acute yellow atrophy of the liver. 
The consistency is usually lessened, though associated fibrosis may 
render the affected part abnormally dense. The specific gravity of the 



» 

.; . .v •* 
•«• ••«•• .#* vr •• • !•• 



Fig. 13. — Fatty degeneration of the epithelium of the renal tubules; stained with osmic 

acid (Simmonds). 

tissue is notably reduced. In the nervous system and in caseation and 
allied conditions liquefaction may occur. The color in typical instances 
is a pale yellow; the existence and degree of congestion, pigmentation, 
jaundice, or other associated conditions will obviously alter the color. 
The areas of degeneration may be uniform or isolated. In the heart 
and liver particularly streaks or irregular areas may 
produce a mottled appearance. On section, free fat 
may drip from the knife and cut surface; in other cases 
no fat-droplets can be seen macroscopically. In rare 
instances fat-crystals may be visible to the naked eye. 

Microscopical Appearances. — The parenchyma cells 
are first and most extensively affected, though the con- 
nective tissue may become involved. The cells are 
usually somewhat enlarged. The natural granules of 
the protoplasm disappear, and in their stead are fine 
dark granules, which usually stain black with osmic 
acid (Figs. 13, 14), and which are dissolved by alco- the heart muscle, 
hoi, ether, etc., but not by acetic acid. A peculiar 
reaction of the granules is their staining with fuchsin (fuchsinophile 
granules). Usually the granules are very fine and only slightly refrac- 
tile; they may, however, be large, and considerable droplets may appear 
or the entire cell become one large fat-drop, as in fatty infiltration. 




Fig. 14.— Fatty 



84 



A TEXT-BOOK OF PATHOLOGY 



The nuclei in many cases of moderate degree show no changes; later in 
the process, however, the chromatin becomes diffused and refuses to 
stain and the nucleus may entirely disappear. When the fat is dis- 
solved out of the cell a vacuolated protoplasm may be observed. In 
early stages the protoplasm has been asserted to be unaltered when thus 
examined. The cell membrane sooner or later breaks down, and the 
fatty contents and detritus fill the space. Cholesterin, lecithin, and 
fatty crystalline formations are often seen. 

Seats. — Fatty degeneration occurs in nearly all tissues. The epi- 
thelial structures, especially the liver and kidneys, the heart muscle, 
and the central nervous organs are the tissues most frequently affected. 
As before stated, interstitial as well as parenchymatous tissues may be 
involved. The cellular constituents of exudates and transudates are 
also liable to the change, and the liquid may thus present the appearance 
of an emulsion. 

Pathological Physiology. — Recent investigations tend to destroy 
the old theory that fatty degeneration results from a transformation of the 
protoplasm of cells into fat. Investigations have shown that the cells 
of many of the tissues and organs, notably glands, contain fat, and that 
this is undoubtedly derived from the blood, also that the fat in true 
fatty infiltration has the same origin. In so-called fatty degeneration 
the protoplasm is diseased and in advanced stages completely de- 
stroyed. This would seem to sustain the old view of direct transforma- 
tion of protoplasm into fat; but the most accurate chemical investigations 
do not confirm the possibility of such a transformation. Further, when 
animals were poisoned with phosphorus and a fat foreign to the animal 
was administered the fatty organs contained the foreign fat. These 
considerations have led to a quite general belief that fatty degeneration 
results from an infiltration of fat derived from the blood and remotely 
from the fat deposits of the body or from food. The significant difference 
between fatty infiltration and fatty degeneration is that the former is a 
deposition of fat in otherwise normal cells as a result of excessive supply 
of fat, or possibly a lowered metabolic activity which normally disposes 
of fat, while the latter represents a deposit of fat in a diseased cell, the 
disease inviting the deposition or greatly reducing the capacity of the 
cell to dispose of fat even in normal quantities. For these reasons the 
terms "fatty infiltration" and "degenerative fatty infiltration" have 
been suggested for the respective conditions. It seems certain that to 
some extent at least the granular and molecular fat contained in cells 
the seat of "fatty degeneration" represents normal fat of the cells which 
had previously been in some form of combination and invisible, but as 
a result the degeneration became free and visible. This view has been 
expressed by a number of pathologists and has some experimental 
support. 

In some experiments in which starving frogs were poisoned with 
phosphorus the direct conversion of protoplasm into fat seemed to have 
been demonstrated, but even in these experiments the glycogen of the 
liver may have been the source of the fat produced, and, besides, ob- 



RETROGRESSIVE PROCESSES 



85 



jection has been raised against the chemical methods relied on in these 
experiments, 

It would seem probable that both factors may be active in some 
cases, but Wells maintains that in kidneys and muscles the metamor- 
phosis of intracellular fat is more important than absorption. In 
either case it is to be assumed that the enzymic power of the cells has 
been damaged. 1 

Fatty degeneration tends to cause secondary changes in the proto- 
plasm of the affected cell, or the degeneration which in the first instance 
underlies the condition tends to increase until the cell is practically de- 
stroyed. Cellular function is, therefore, eventually impaired or per- 
verted, but experiments have shown that considerable fatty degenera- 
tion of the heart muscle may exist without impairment of the heart's 
power (Romberg, Krehl). The same may be true of other organs. Mild 
grades, with preservation of the nuclei of the cells, admit of recovery; 
severe grades go on to total necrobiosis. 

Lipoid metamorphoses are found either as infiltrates or degenera- 
tions in cancer necroses, atheromatous blood-vessels, and syphilitic 
lesions. They were formerly considered fatty, but it is now strongly 
suspected that they have to do with protein destruction. The lipoids 
are commonly found as cholesterol esters and appear as doubly refrac- 
tile or cuboidal crystals under the polarizer. 

THE ALBUMINOID DEGENERATIONS 

The hyaline, mucoid, and colloid degenerations represent protein 
metamorphoses which are closely related. In typical instances they can 
be quite clearly differentiated from each other, and for the sake of clear- 
ness and convenience they will be separately described. It must be 
understood, however, that the products are closely related substances 
whose chemical characteristics and relations are not clear, and which 
cannot in many cases be distinguished. 

HYALINE DEGENERATION 

Definition. — This term probably comprises a group of retrogressive 
processes characterized by the appearance of a clear, firm, homogeneous 
protein substance of obscure nature. It is probable that various proc- 
esses, defined as hyaline, may have entirely different characters. 

1 A. E. Taylor while engaged in systematic analyses of the liver and kidneys in 
fatty degeneration noticed that these degenerated organs retained less of their fat on 
etheral extraction than do normal organs. He, therefore, carried out experiments on 
frogs by producing a fatty degeneration with phosphorus and extracting the fat, 
which was then compared with that from normal frogs. As a result of his experi- 
ments he offers the hypothesis that the combined fat is a metabolic constituent of the 
protoplasm of the cell. During the course of the disease causing the fatty degenera- 
tion this combination is broken after the manner of the action of ferments, and the 
previously combined fat is set free, when it appears as fatty granules in the proto- 
plasm. Following this comes fat transportation and infiltration of the affected cells. 
The reason for such infiltration is, however, not understood. 



86 



A TEXT-BOOK OF PATHOLOGY 



Certain cases are allied to amyloid, mucoid and colloid metamorphoses, 
and some to coagulation necrosis. The hyaline change of epithelium 
of older authors is now, by general consent, classed as a mucoid trans- 
formation. 

Etiology. — Hyaline degeneration occurs under the following patho- 
logical circumstances: in the muscles during infections and septic proc- 
esses and following traumatism; in intoxications, as by lead; in inter- 
stitial hemorrhages and hematoma ; in struma ; in cicatrices ; in the blood- 
vessels in old age, arteriosclerosis, or aneurysm; in all forms of arteritis, 
especially in vessels of the nervous system; in the endocardium and cardiac 
valves in all diseases affecting them; in the granulomata; in neoplasms, 
especially cylindromata and keloids; in the lungs in pneumonia; in the 



' ^8 



mem. «S 




Fig. 15. — Cylindroma, showing a number of blood-vessels whose walls have become 
converted into hyaline material. 

kidneys in nephritis; and in all conditions of coagulation necrosis and 
fibrinous exudation, for in these processes hyaline degeneration seems 
to be a factor. Very probably the process is not the same in all of these 
cases, but the similarity of appearance, staining reaction, and general 
pathological behavior prevents a definite differentiation. 

Pathological Anatomy. — Hyaline change is not usually massive 
enough to be macroscopically appreciable. When so, the organ or tissue 
is enlarged, dense, and presents a pale, homogeneous, opaque appear- 
ance. Upon the mucous and serous membranes small collections may be 
readily seen, and may present either a pseudomembranous appearance 
or may occur as opaque plates upon or beneath the surface. Micro- 
scopically, there are three chief sites: (a) In the blood-vessels, where the 
degeneration may appear in the endothelium, beneath it, between the 



RETROGRESSIVE PROCESSES 



87 



coats and fibers of the vessel, or surrounding the vessel. The wall is 
thickened, the lumen is narrowed or obliterated; the endothelium may be 
loosened or in a state of proliferation. Perivascular hyaline change is 
well seen in certain tumors — cylindromata (Fig. 15). (6) In the inter- 
stitial tissues, as between the muscle-fibers, the hepatic cells, the renal 
tubules, in the reticulum of lymph-glands, in the retina, and in neo- 
plasms and cicatrices. It may be uniform in distribution, but is more 
often irregularly clumped or may be in concentric whorls. In tubercu- 
lous foci the reticular fibrillar become swollen and gelatinous in appear- 
ance. They may swell to such a degree that the whole focus has a 
uniformly waxy appearance, the cells enclosed in the meshes meantime 
undergoing complete necrosis. In scleroses, as in the liver, the newly 
formed connective tissue may assume a hyaline character, the fibers 
being so closely packed together and transformed that the mass has a 
homogeneous appearance, (c) Within the cells. This condition is 
probably limited to mesodermic cells. It may be seen in muscle and 
giant cells, and in endothelium, leukocytes, or wandering cells to a less 
degree. Whether the epithelial cells take part in this transformation 
in the coagulation necrosis of mucous membranes and in the produc- 
tion of casts in nephritis has not been decided. It has not been possible, 
in the intercellular or interstitial varieties, to decide whether the sub- 
stance was formed there or deposited there; in the vascular form, and 
especially in coagulation necrosis and fibrinous exudations, it is prob- 
able that it is formed in loco. 

"Hyaline thrombi" cannot be distinguished in their appearance from 
hyaline masses elsewhere. Whether or not they are examples of true 
hyaline material is uncertain. 

Russell's Fuchsin Bodies. — These are round bodies, of variable size, 
situated within or between the cells of epithelial tumors or many normal 
tissues. They resemble hyaline material in appearance and staining 
reactions, especially in their affinity toward acid fuchsin. 

Unstained, hyaline substance has a glistening, waxy appearance; 
it is less translucent than amyloid. Typically it evinces an affinity 
for the acid anilin stains. Stained with van Gieson's mixture of picric 
acid and acid fuchsin, the hyaline substance takes on a brilliant red 
color. It may or may not take the fibrin stains; it often takes basic 
stains in a modified manner. In truth, the reactions of hyaline material 
are very uncertain and shifting: in many instances it can scarcely be 
distinguished from amyloid, and the change is then called hyalo-amyloid ; 
in other instances the product closely resembles mucin and the colloid 
substance. The cells of affected parts often show fatty degeneration or 
other alterations. 

Seats. — The locations most often affected are the muscles, especially 
the recti abdominalis in typhoid or other fevers, the mucous membranes, 
the liver, kidneys, ovaries (corpora lutea in particular) and adrenal 
bodies, the cardiovascular system, the nervous system, the serous 
membranes, and the retina and choroid coats of the eye. The other 
locations are suggested in the discussion of the etiology. 



88 



A TEXT-BOOK OP PATHOLOGY 



Pathological Physiology. — Von Recklinghausen believed it to be a 
coagulation of normal protein upon the death of the cells; this explana- 
tion is, however, insufficient. It appears more likely either that it con- 
sists of protein modified in loco by disturbed action of cells, or that it is 
a deposition by cellular carriers of insoluble material formed elsewhere. 
The exact nature of the transformation is entirely obscure; it cannot be 
held analogous to the coagulation of proteins by heat; nor to the pre- 
cipitation by metals or salts, since in these events the proteins are not 
usually rendered permanently insoluble in water and are in other ways 
clearly different. Hyaline material can undoubtedly be reconverted, 
absorbed, and removed. Its presence rarely compromises the paren- 
chymatous structures to an extreme degree. 

MUCOID DEGENERATION 

Definition. — Theoretically, this is the conversion of cellular pro- 
toplasm into mucin. Mucin is a glycoprotein which contains no phos- 
phorus, and which by virtue of its carbohydrate moiety reduces cupric 
sulphate in alkaline solution. Chondroitin sulphuric acid has been 
found in some mucins, showing the relationship of this albuminoid 
degeneration to amyloid infiltration. It is quite insoluble in water, 
but has itself a marked capacity for taking up water. It is very soluble 
in alkaline solutions, but is precipitated by saturations with most neutral 
salts. It is precipitated by acetic acid from solutions poor in salts; also 
by heat, alcohol, and many of the metals. It does not dialyze. The 
secretions from different classes of epithelium differ notably among 
themselves, and the pathological mucins differ still more. 

Etiology. — Mucoid transformation should be distinguished from 
hypersecretion of mucin. Hypersecretion is a common result of in- 
flammation or irritation of all sorts; it is seen in the pulmonary, gastro- 
intestinal, and urinary mucous membranes, in the glands of Cowper, 
the gall-bladder, the salivary glands, in the antrum of Highmore, in the 
lacrimal glands, and in the testicles. The product of the epithelium of 
the urinary tract and gall-bladder, usually called mucin, is more often 
nucleo-albumin. Mucoid degeneration, in the strict sense, occurs most 
frequently in mesoblastic tissues, the abnormal substance lying be- 
tween the cells. It is in some way connected with inflammatory proc- 
esses, as, apart from its occurrence in tumors, it is found only in tissues 
the seat of inflammation. Any of the connective tissues of the body may 
be affected. Widespread myxomatous degeneration of the subcutaneous 
tissues may be seen in myxedema. In some cases of myxedema, sclero- 
derma, and the other pachydermic affections mucin has been extracted 
from the skin; other attempts in similar cases have failed. Neoplasms 
comprise the third group of conditions presenting mucoid phenomena. 
The transformation occurs in sarcomata, carcinomata, fibromata, lipo- 
mata, chondromata, and especially in the myxomata, in which mucin is 
the essential element, while in the other growths it is an accidental and 
occasional transformation. In the epithelial tumors the epithelial cells 
themselves may be affected. 



RETROGRESSIVE PROCESSES 



89 



Pathological Anatomy. — The gross appearances may consist in 
nothing but the appearance of the mucin. Upon catarrhal mucous 
membranes is a coat of thick, tenacious mucus, with or without con- 
gestion or other changes. In localities where the mucin becomes pent 
up it swells markedly, dilates the containing spaces, flattens the epithe- 
lium (which may then atrophy), and later becomes converted into a 
simple albuminous fluid. Such a process is seen in the antrum of High- 
more, in Cowper's glands, in the salivary glands, in the gall-bladder, in 
the vermiform appendix, etc. ; in these cases the appearances are those of 
a cyst. In mucoid degenerations in the connective tissues the appear- 
ances are often not characteristic of mucin; the tissues are soft and 
elastic and tear easily. In tumors, cysts are usually formed along with 
diffuse mucoid infiltration. In cystic ovarian neoplasms the produc- 
tion is often massive, and the substance is often peculiar in refusing 
precipitation by acetic acid, and has, therefore, been termed "pseudo- 
mucin." In myxomata the substance is usually much more dense. 

Microscopical Appearances. — In ca- 
tarrhal mucous membranes the goblet- 
cells are seen in excessive quantity. 
Only in extreme instances is the process 
accompanied by the death of the cell. 
The cells are much swollen, and the dis- 
tal end is especially bulged out with its 
drop of mucin. There is usually a sub- 
mucous inflammatory reaction, and pus- 
cells containing mucoid material may be 
seen. In the connective tissues it is 
seen that the mucin lies between the 
cells and that the ground substance has 
disappeared — i. e., been converted into 
mucus (Fig. 16). The cells very rarely 
present mucous change, but are often 
degenerated in other ways. In tumors 
the change may occur in and between the cells and in the form of 
cysts, whose walls may or may not present a cellular lining. The 
blood-vessels are rarely affected. In all situations mast-cells may be 
seen, often abundantly. 

Mucin is best fixed with corrosive sublimate. As a rule, it elects basic 
stains. It stains only moderately with hematoxylin, but very well 
with methylene-blue and, indeed, with most of the basic anilin stains. 
Thionin and toluidin-blue are the best stains, giving it a purple-red color. 
These staining reactions are not entirely distinctive, and it is often im- 
possible to differentiate mucoid from colloid material, and even from 
hyaline and amyloid material. 

Seats. — Of normal epithelial tissues, the mucosa of the respiratory 
and gastro-intestinal tracts, the salivary glands, and the uterus are most 
often affected; any epithelium may, however, be involved. The con- 
nective tissues have been sufficiently considered. Of neoplasms, ovarian 




Fig. 16. — Myxomatous degenera- 
tion of a sarcoma, showing stellate 
cells separated by mucoid intercellu- 
lar material (Karg and Schmorl). 



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A TEXT-BOOK OF PATHOLOGY 



cysts, abdominal carcinomata, and mesoblastic tumors anywhere are 
most liable. 

Pathological Physiology. — Since the deposition of mucin seems to 
be excluded, the only explanation is to assume the conversion of other 
proteins into mucin. The causes and modus operandi are not clear; the 
fact, however, that in the cysts the mucin may be reduced to simple 
albumin shows the possibility of such transformations. 

Unless the disease is very prolonged, affected mucous membranes 
may recover. The connective-tissue forms do not of themselves threaten 
the life of the tissue; and the deposit is often removed by reabsorption. 
In neoplasms the degeneration seems an evidence of cell death. 

COLLOID DEGENERATION 

Definition. — This consists in the abnormal appearance of a sub- 
stance whose physical prototype is the colloid material of the thyroid 
gland. It is not precipitated by acetic acid or alcohol, does not take 
up water avidly, and is, therefore, much like the pseudomucin already 
noted. 

Etiology. — It occurs in goiters and in thyroid neoplasms, in the 
hypophysis cerebri, in the kidneys (some cases of congenital cysts) 
and the adrenal bodies, in the prostate and seminal vesicles, in the 
atrophic gastric mucosa, in cysts of the lips and larynx, and in the 
cervix uteri. Colloid transformation in neoplasms apart from those of 
the thyroid body is very rare. The natural and increased colloid of 
the thyroid gland, and sometimes that found in the hypophysis, con- 
tains iodin, associated with a globulin and a nucleoprotein. Because 
of the absence of iodin in other so-called colloid conditions, cancers and 
cysts, many authorities restrict the word "colloid" to the iodin-contain- 
ing kind of the thyroid, and call the homogeneous metamorphosis in 
cancers mucoid. Colloid is believed to be a direct product of altered 
cell metabolism, and, aside from the thyroid, is usually mucin, pseudo- 
mucin, or some other protein which has assumed a jelly-like form in a 
tightly closed space. There is no uniform organic chemical substance 
that may be identified as colloid. 

Pathological Anatomy. — Affected organs may be enlarged and may 
be hard or quite soft. On section, the colloid areas appear as yellowish- 
brown, translucent bodies; rarely they are arranged in large clumps. 
They may be macroscopically invisible or, on the contrary, may form 
large cystic collections with thin, flattened walls. Colloid degenera- 
tion may be accompanied by serous transudation, due probably to 
vascular disturbances. The serous transudation seems to dissolve the 
colloid material, so that finally the cysts form compartments filled with 
a chocolate-colored fluid containing pus, blood, and crystals of choles- 
terin, sodium chlorid, and calcium oxalate (Fig. 17). 

Microscopically, the material is found in the glandular acini, in 
the cells, and in the connective tissues. There are often signs of pres- 
sure, and, probably from the same cause, the areas are anemic and have 



RETROGRESSIVE PROCESSES 



ill 



a poor vascular supply. The arrangement is usually in balls or whorls, 
homogeneous as a rule, but often with concentric or radiating lines. 
The areas often intercommunicate, and extensions may be traced into 
the adjacent tissues. The cells usually show degenerative changes, and 
inflammatory reactions are often present. Crystals of calcium oxalate 
are common. Acid stains are usually elected, as in hyaline degeneration. 
The indefiniteness of the reactions may make it impossible to exclude 
hyaline and mucoid changes. 




Fig. 17. — Colloid degeneration of the thyroid gland, showing masses of colloid matter in 
the gland acini (Karl and Schmorl). 

Pathological Physiology. — This is obscure, but seems to be analo- 
gous to that of mucoid change. The substance is undoubtedly produced 
in loco. 

Colloid is a grave degeneration, usually connected with marked 
cellular disturbances. 

AMYLOID INFILTRATION 

Definition. — Amyloid deposits are nowadays thought infiltrative, 
although formerly regarded as degenerative. Amyloid, a name given by 
Yirchow because of certain reactions suggesting starch, is not a starch, 
but a glycoprotein, an abnormal combination of chondroitin sulphuric 
acid, such as is normal in tendon, with a protein. The exact chemistry 
is not known and the combination is believed to be due to faulty 
metabolism in loco. It differs from most retrogressive changes in that 
it affects the interstitial tissues, and not the cellular contents. The 
presence of balls of amyloid within cells has been maintained by some 
authors. The names "lardaceous disease" and "lardacein" are used by 
some writers, denominations warranted by the gross appearance at least. 

Amyloid disease may be local or general, the latter being called 
"amyloidosis." 



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A TEXT-BOOK OF PATHOLOGY 



Etiology. — The common conditions under which amyloid infiltra- 
tion arises are prolonged suppuration and ulceration. In tuberculosis, 
especially of the lungs and skeleton, particularly in cases of mixed 
infection and in syphilitic ulceration, are found the conditions most 
favorable to its production. It occurs, however, in connection with 
ulcerations of various sorts, gastro-enteritis, and actinomycosis. Rarely 
it occurs under conditions of cachexia without suppuration, as in cancer, 
malaria, leukemia. Sometimes it is found without any apparent cause. 

Certain local "amyloid" formations {corpora amylacea) are probably 
in nowise connected with the general condition and, undoubtedly, are 
often entirely physiological. Their relation to amyloid disease is doubted 
by many, but they do give modified iodin and gentian-violet tests. 
It is said that they grow by deposit of crystals containing some protein. 




Fig. 18. — Amyloid degeneration of the kidney, showing amyloid substance in the walls 
of the blood-vessels of the glomerulus at b, and hyaline tube-casts in the renal tubules 
at a, g (Ziegler). 

Pathological Anatomy. — In marked instances the organs are en- 
larged and their specific gravity increased. On section, the tissue is firm; 
the cut surface is smooth and neither contracts nor extrudes. The 
consistency varies with the coexistence and degree of fibrosis, fatty 
degeneration, etc. Amyloid substance is more inelastic than any other 
infiltrative material. The color of the organ is usually pale, but may 
obviously be altered by congestion, pigmentation, or fatty degeneration. 
The amyloid substance itself has a glistening, waxy, translucent appear- 
ance which is almost pathognomonic. This waxy appearance is not al- 
ways uniform. Slight or even moderate degeneration may not occasion 
macroscopical appearances; in fact, apparently quite normal tissues may 



RETROGRESSIVE PROCESSES 



93 



be highly amyloid microscopically. The special appearances in various 
organs will be described in the appropriate chapters. 

Lipoid or actual fatty deposits are found associated with amyloid 
infiltration, especially in syphilitic conditions. They are either deposits 
from body fluids or arise from tissue degenerations in the vicinity. 

Microscopical Appearances. — The favorite seats are the outer surface 
of capillary blood-vessels and the intima and media of larger blood- 
vessels, the adventitia being rarely affected, the endothelium apparently 
never. The fixed connective tissues of the organs, elastic tissues, and 
basal membranes of glandular acini, or between them and the gland 
cells, are the parts affected, the wandering cells and leukocytes being 
rarely involved. Muscle cells are undoubtedly susceptible; but recent 
studies seem to show that glandular and lining epithelium is never 
involved. Such cells may, and often do, show fatty or other degenera- 
tions or necrosis, but the presence of amyloid substance within their 
protoplasm has not been shown. The substance appears as irregular 
clumps or streaks in the interstitial tissues, often compressing the 
cells and blood-vessels. It presents a glistening, homogeneous appear- 
ance. The cells usually present evidences of atrophy and other de- 
generations. In the renal glomeruli and in the Malpighian corpuscles 
of the spleen the appearances are perhaps most distinctive. Without 
staining, amyloid degeneration cannot always be distinguished from 
other degenerations; indeed, not always with staining reactions. The 
substance is highly resistant to bacterial decomposition and to diges- 
tion. 

Reactions. — (See also below.) The gentian-violet reaction seems to be 
the most invariable. In sections of tissue fixed (preferably in alcohol) 
for microscopical study gentian-violet colors the normal tissues blue ; the 
amyloid substance is a light pink or red. Iodin-green gives a similar 
red reaction. A mahogany-red reaction with Lugol's solution of iodin 
is quite constant, but fails in the isolated amyloid bodies. It is easily 
obtained in fresh specimens freed of blood. The red color is changed 
to a blue by treating with sulphuric acid or chlorid of zinc. 

Seats. — In the order of frequency amyloid degeneration affects the 
kidney, liver, and spleen, then the larger blood-vessels, the intestinal 
mucosa, the lymph-glands, the skeleton, the adrenal bodies, and the 
heart. It rarely affects the pulmonary mucosa, the bladder and genitalia, 
the thyroid body, the voluntary muscles, and, apart from the local amy- 
loid bodies, the nervous system or the integument. 

Local Amyloid Formations. — These occur in the nervous system, 
especially in advanced years and in scleroses, grouped about the blood- 
vessels, and most marked in the posterior cord and in the brain; in 
the prostate gland; about inflammatory areas; in infarcts; in granulo- 
mata, especially syphilis; as tumor-like swellings in the upper air- 
passages, and in neoplasms. They present themselves as small round 
bodies which usually have a concentric arrangement resembling starch 
granules. They do not usually present the typical amyloid reactions; 
often they react more like hyaline substance, and, indeed, the blood- 



94 



A TEXT-BOOK OF PATHOLOGY 



vessels of the affected part seem especially affected with hyaline change. 
Ribbert says the small vessels are curiously free from change. The 
neighboring lymph- vessels and glands are usually attacked. The 
special appearances and reactions of the amyloid bodies of the nervous 
system will be described in connection with Neuropathology. 

Pathological Physiology. — As stated, amyloid substance seems to 
be a combination of chondroitin sulphuric acid with a protein. It is 
composed of hydrogen, nitrogen, carbon and sulphur, and is insoluble 
in weak alkalies. Chondroitic acid is normally present in bones, carti- 
lages, and elastic tissue. It seems to have been shown that an amyloid- 
like substance exists in the elastic coat of the blood-vessels — perhaps a 
different combination of chondroitic acid. Our present knowledge sug- 
gests that amyloid substance is not entirely abnormal, but rather an 
abnormal combination of normal substances. It seems to result from 
protein alterations in connection with the pathological processes already 
detailed, having as a result the liberation of large amounts of chondroitin 
sulphuric acid. That bacterial influences are not necessary is suggested, 
though not proved, by the fact that amyloid change has been produced 
by long-continued aseptic suppuration induced by turpentine injection. 
Amyloid change is an infiltration, the constituents being deposited from 
the blood and assuming their peculiar characters locally, for amyloid 
is not found preformed in the blood itself. Possibly local cellular condi- 
tions favor the deposition by reason of a loss of power to dispose of the 
constituent substances brought by the blood. Hyaline degeneration 
seems at times a preliminary stage in the process. 

Amyloid degeneration interferes with functional activity by pres- 
sure upon the parenchyma and by vascular disturbances. By its situa- 
tion in and around the blood-vessels it may occasion thrombosis. Reab- 
sorption of amyloid substance is possible, as it has been known to occur 
when part of the diseased area has been extirpated. Such reabsorption 
does not, however, occur when extensive amyloid change exists. 

GLYCOGENIC INFILTRATION 

Definition. — This condition consists in the presence of glycogen in 
cells which normally contain none, or the presence of an excess in cells 
which normally contain it, as in the liver, cartilages, muscles, leukocytes, 
in the embryo in all tissues, and in the uterus. The attempt has been 
made to separate glycogenic infiltration from a glycogenic degeneration, 
but the conversion of protoplasmic protein into glycogen has never been 
demonstrated. 

Etiology. — The condition is not infrequent. It is seen in the tissues 
in diabetes, especially in the kidneys (Henle's loop in particular), 
muscles, liver, and circulating leukocytes. It occurs in neoplasms, 
especially in malignant growths of mesoblastic origin, being rare in 
most carcinomata. It may be said that the more cellular the tumor, 
the more the glycogen, except in carcinomata, where the amount is small 
and variable. In leukocytosis of different varieties the cells may con- 



RETROGRESSIVE PROCESSES 



95 



tain granules of glycogen or a substance resembling glycogen, and 
similar granules may float free in the plasma (see Iodophilia). In puru- 
lent collections and in inflammatory areas the cells may be markedly 
infiltrated. The infectious granulomata, however, seem exempt. The 
amylaceous bodies of the prostate are closely allied to glycogen. 

Pathological Anatomy. — Tissues rich in glycogen may present a 
hyaline appearance; usually there are no macroscopical alterations. 
Microscopically, the material is generally found within the cells; it may, 
however, be in the intercellular substance, and may be free in the plasma 
of blood or the fluid of exudates. It is commonly deposited as round 
balls, which may be concentrically striated. In fresh tissues it is soluble 
in water, but loses its solubility after fixation by alcohol, etc. Tissues 
to be studied for glycogen must be fixed in absolute alcohol, since watery 
solutions add a molecule of water to the glycogen and change it to sugar, 

C 6 H 10 O 5 + H 2 = C 6 H 12 6 . 

Glycogen is stained brown by iodin, but the brown is not turned 
blue on the application of sulphuric acid. Ptyalin or amylopsin con- 
verts glycogen into sugar, with the loss of the color-reaction. 

The pathological physiology is obscure. In diabetes it is simply 
an expression of the general hyperglycemia. At the end of long exhaust- 
ing diseases glycogen may not be found in the cells. The cells are 
left swollen. In neoplasms and suppurations the collections are prob- 
ably depositions. 

DROPSICAL INFILTRATION 

By dropsical infiltration is meant edema of the cells, the presence 
in cells of an excess of plasma. It may be considered as of two kinds: 




b 

Fig. 19. — Dropsical infiltration of the epithelial cells of a carcinoma of the breast: a. 
Ordinary epithelial cells; 6, b, dropsical cells; c, dropsical nuclei; d, enlarged nucleoli 
(Ziegler) . 

(a) Dropsical degeneration, a fine granular disintegration of the cyto- 
plasm preceding or associated with cloudy swelling, (b) Dropsical 
infiltration, grosser collections of vacuoles or droplets of fluid disturbing 
the general architecture. This does not always occur in general dropsy, 



96 



A TEXT-BOOK OF PATHOLOGY 



the fluid being between the cells and often compressing them to a 
marked degree. In other instances the cells take up the fluid. In burns 
and pemphigus and in other skin lesions presenting vesiculation, and 
in various inflammations of organs, edema of the cells occurs. It is 
also a part of the degeneration termed "cloudy swelling." 

The cells are enlarged, often to an extreme degree, and they may 
even burst. The protoplasm sooner or later becomes cloudy and often 
presents degenerative changes — fatty metamorphosis in particular. 
Vacuolation is frequently observed (Fig. 19). 

The condition is probably a purely physical phenomenon in the 
dropsies. In the cutaneous lesions other factors are operative. The 
diffusion of water into the cell may be explained by a toxic disturbance 
of the internal chemistry with an increase of crystalloids which attract 
water. 

CALCIFICATION 

Definition. — Calcification consists in the abnormal deposition in 
tissues of earthy salts, without organization and the anatomy of bone. 
It may be considered as evidence of local or general senescence, but 
is never a primary process. The phosphates and carbonates of cal- 
cium are the chief salts concerned; oxalates, however, are often 
present; and the corresponding magnesium salts may be mixed with 
them. The best physiological examples are the senile change in' the 
vascular apparatus and the formation of the brain-sand (acervulus 
cerebri). Calcification of the skeletal tissues is usually accomplished as a 
physiological process through the activities of special cells; this is an 
essential element in ossification. 

Etiology. — The deposition generally occurs in diseased tissues, 
especially in those the seat of vascular disorders. Local necrosis or 
fibrosis antedates intercellular calcification, and the process may be 
accompanied by atrophy and absorption of certain cellular elements. 
In neoplasms, abnormal cellular conditions certainly predispose; but 
here, too, the vascular relations are of notable importance. Hyaline 
and fatty degenerations often precede or accompany calcification. 

In rare instances no local predispositions can be determined. Cases 
of this kind occur in old age, and in these cases it is inferred that, owing 
to increased lime-resorption from the skeleton, the system is saturated 
to the point of precipitation (metastatic calcification). Similar super- 
saturation of the blood with calcareous matter may occur in cases of 
extensive disease of bones, and may lead to widespread deposition. 
It is noteworthy that the precipitation of the bone salts circulating in 
excess occurs most frequently where acid is excreted — lung, stomach, 
and kidney. Local anemia favors calcification. 

v. Kossa found that corrosive sublimate, acetate of lead, copper 
, salts, iodin, and iodoform all are capable of producing calcification 
experimentally. 

Pathological Anatomy. — Early in the process no macroscopical signs 
are apparent. On microscopical examination the salts are seen as fine gran- 



RETROGRESSIVE PROCESSES 



97 



ules scattered through the intercellular substance. Cellular infiltration, 
however, is not uncommon, and in such instances the cells show more 
or less extensive nuclear and protoplasmic degenerations. By the 
coalescence of the granules larger, irregularly spherical bodies may be 
formed. These usually have a concentric arrangement (psammoma 
bodies). Definite crystals are rare, but may be seen. The next adjacent 
tissue may present an opaque appearance. In certain localities, espe- 
cially the blood-vessels and serous membranes, calcareous plates are 
formed. The depositions may attain a surprising size, especially in the 
vessels and in neoplasms. The color of the deposits is usually white, 
grayish, or yellow; accidental pigments may, however, produce dis- 
colorations. On staining, the deposition takes up both carmine and 
hematoxylin, but exhibits no elective attraction for the anilin dyes. 
The salts are dissolved by acids, best by hydrochloric acid; in the case 
of carbonates, with evolution of carbonic acid gas. Fibrosis, cellular 
necroses, and degenerations can be demonstrated in the tissues by suit- 
able methods. 

Seats. — It is in the cardiovascular system that the condition is 
of the most importance. It often occurs as a simple senile change, 
usually connected with an atrophy of the elastic tissues of the vessel 
walls, hyaline degeneration of the connective tissue, and general fibrosis. 
It is almost invariably an accompaniment of sclerotic endocarditis and 
arteriosclerosis. In the endocardium the valves are most frequently 
affected; of the vessels, the aorta, the coronary arteries, and the cerebral 
vessels. The process is, however, often universal, and the splanchnic 
vessels and radial arteries seem very susceptible. It affects chiefly the 
intima and media. In the pericardium the deposition is uncommon 
without the previous occurrence of pericarditis; in adherent pericar- 
dium the heart may be literally enclosed in a calcified sac. In the myo- 
cardium calcification is usually interfibrillar, but may involve the fibers. 
Large collections may occur in the pituitary body, the meninges, and in 
the ventricular plexuses. It is common in the joints, uncommon in the 
pleura, rare in the peritoneum. In the muscles local formations are not 
rare, and usually occur at the seat of previous injury or irritation. In 
the lungs and liver it is not unusual in and around foci of necrosis due to 
various causes (tuberculosis, parasites, etc.). Cicatricial tissue often be- 
comes calcified. In the walls of cysts, in the biliary and urinary bladders, 
in the limiting wall of old abscesses and hematomata, in thromboses, 
and even in cutaneous scars calcification, as a crust or infiltration, is a 
common incident. In the kidneys infarcts of these salts may be formed. 
The neoplasms most subject are the avascular tumors: uterine fibro- 
mata, fibromata in general, dermoid cysts, goiters, scirrhous carcinomata, 
tumors of the pituitary bodies, and especially neoplasms involving bones 
or cartilages. It may, however, occur in the most vascular sarcomata. 
The special term "psammoma" (q. v.) is applied to certain calcified neo- 
plasms. Lithopedia are the calcified fetuses of extra-uterine pregnancy. 
Apart from neoplasms, the most striking intracellular depositions are 
seen in the ganglion-cells in areas of softening and in the renal cells 

7 



98 



A TEXT-BOOK OF PATHOLOGY 



following certain metallic poisonings (mercury). It is interesting to 
note that the intestinal epithelium, which normally secretes the larger 
part of the lime-salts discharged from the body, is rarely infiltrated by 
them. 

Pathological Physiology. — It seems probable that calcium is car- 
ried in the blood, in the form of tribasic calcium carbon phosphate, by 
the agency of the proteins with an appropriate amount of carbon 
dioxid. In both normal and pathological bone salt deposit there 
seem to be two forces at work, a local chemical condition favoring the 
precipitation of the least soluble crystalloids from the blood and the 
existence of some tissue element having an affinity for calcium. The 
latter factor has been said to be phosphoric acid by some writers and 
ascribed to physical factors, such as the concentrated colloid of car- 
tilage, by others. The local chemical changes favoring calcium deposit 
are said to be a decrease in protein concentration when the tissue 
pabulum is thoroughly used up in loco, and increased alkalinity with 
decreased carbon dioxid. There is, however, some experimental evi- 
dence to show that the fatty acids formed in necrobiotic tissue combine 
with calcium to form soap, the combined acid later giving way to acid 
radicals of stronger affinity for the base, carbonic and phosphoric. It 
must not be forgotten that we are dealing with a secondary process in 
a tissue whose metabolism is not and has not for some time been normal. 

Calcareous deposits are probably never removed, but once formed, 
remain permanently. There is no doubt that they influence the ad- 
jacent tissues, causing degenerations. 

OSSIFICATION 

This term implies the deposition of lime-salts and other changes 
through the agency of osteoblastic cells. It occurs in cartilages and in 
tumors connected with the bones, cartilages, and periosteum. Ossifica- 
tion of the muscles may occur as a local process or as a widespread and 
progressive disease. (See Myositis Ossificans.) The salts are regularly 
deposited and are usually in masses between the cells. An accurate 
differentiation from calcification can in some instances be made only 
by the detection of osteoblasts after decalcification of the material. 
The essential difference lies in the fact that in ossification an attempt 
is made to reproduce the architecture of bone. 

URATIC INFILTRATION 

Deposits of urate of sodium in the cartilages and fibrous tissues of 
joints and in various other situations occur in the course of gout. (See 
Disturbances of Metabolism and Diseases of Joints.) It is not known 
whether this occurs in normal or necrotic tissue, but such a deposit is 
not normal to cells. The urates occur as slender needles. In the kidneys 
of babies shortly after birth there occur deposits of urates, chiefly of 
ammonium, to which the name "uratic infarct" was formerly given. 



RETROGRESSIVE PROCESSES 



!>!) 



This gives a false impression, since it is merely a collection of urates of 
which the kidney cannot rapidly rid itself. 

Cholesterin deposits are not really infiltrations, but result from cell- 
ular degeneration, or some as yet undetermined cause. They appear in 
cysts and tumors, as in the thyroid and in atheroma, as flat, rhombic 
plates with an angular defect in one corner. With sulphuric acid they 
give first a red then a violet color. 

Concrements. — There may collect in bodily or organ spaces, within 
the organs or their tubular entrances and exits, masses of inorganic 
matter. These are called concrements. By this is not meant that 
masses of foreign matter are introduced solely from without, like hair 
balls, but those whose components are recruited from the body fluids. 
Concrements may be started by a nucleus of desquamated covering or 
a product of inflammation, or by concentration, inspissation, or precipita- 
tion of some otherwise normal secretion or excretion. The first is ex- 
emplified by the collection of mineral salts around a bit of vesical 
mucosa that has been separated from the bladder wall or around a mass 
of bacteria clumped in the gall-bladder by the bile, and floating in it. 
The second type is exemplified by collection of urates occurring as 
sand in the urine, with either clumping or growth by accretion. The 
so-called fecal stones arise by stagnation and inspissation of feces, with 
later accumulation of earthy salts. All stones probably have some 
organic matter in them either as a nucleus or caught in their growth. 
Small foreign bodies may penetrate viscera and cavities and form the 
nucleus of a stone. The chemistry of calculi varies with their origin. 
(See Urinary, Biliary, etc.) It has been suggested that the word 
"calculi" be restricted to bodies arising from precipitation of glandular 
secretion, and the word "concrements" to the deposits of calcareous 
matter locally in organ passages, leading to the formation of solid 
masses. This may be convenient, but is apt to lead away from the 
thought that a nucleus of some sort is necessary for concrements. 

PIGMENTATION 

According to the origin and variety of the pigments, pigmenta- 
tions may be divided into four groups: 1, those in which the pigments 
are derived from external sources; 2, those derived from the hemo- 
globin; 3, those derived from the bile; 4, those derived from cellular 
activity within the organism. 

Pigmentation from the Exterior 

Of the first group, those caused by entrance of foreign bodies through 
the air-passages are the most important. The condition now generally 
termed pneumonokoniosis is commonly a disease of occupation. 
Coal, iron, and stone are the most frequent foreign substances inhaled. 
Vegetable particles, as grain-dust and textile fibers, and animal hairs 
and furs, are not uncommonly the cause of such pigmentations. Corre- 



100 



A TEXT-BOOK OF PATHOLOGY 



sponding to the agent, there are such terms as "anthracosis" (coal-dust 
pigmentation), "siderosis" (iron), "calcicosis" (stone), etc. (Fig. 20). 



j 




Fig. 20. — Tuberculosis of the lung, showing anthracotic pigmentations in the lower part. 

Inhaled substances probably do not reach the alveoli, but are caught by 
the bronchial cellular cilia. In part they are coughed up or otherwise 




Fig. 21. — Phagocytic cells of the bronchial secretion (sputum) containing black particles 
of dust and carbon; the cells on the right are stained with methylene-blue (Jakob). 

cast off with the bronchial secretions ; in part they penetrate the bronchial 
walls or are carried by phagocytic cells into the submucosa (Fig. 21). 



RETROGRESSIVE PROCESSES 



101 



They may become deposited in the latter situation, or may be carried in 
the lymphatic circulation to the peribronchial and mediastinal glands, 
the fibrous tissue of the lung, or the subpleural tissues. In rare in- 
stances, supposedly by rupture or inflammation of a lymph-node, the 
pigment finally reaches the general circulation, following which it is 
deposited largely in the spleen, liver, intestinal mucosa, and kidneys. 
In such cases it shows a periarterial deposition in the secondary location. 

Some investigators have attempted to explain anthracosis of the 
lungs by absorption of coal particles through the alimentary tract. 
They assert that the particles pass through the abdominal lymph- 
nodes, up the posterior chain into the mediastinum, and thence to the 
lung. They would use this reasoning also to explain the course of in- 
fection in pulmonary tuberculosis. The theory is not widely accepted. 

Pigmentation through the alimentary tract is well illustrated by 
argyria following the excessive ingestion of soluble salts of silver. 
The depositions seem to consist of a reduced form of a silver albuminate. 
In the skin the pigment lies directly under the epithelial layer, between 
the cells, and in the intercellular tissue and lymph-spaces. The gastric 
and intestinal walls are deeply affected. The liver and kidneys are usu- 
ally involved; in the former the deposition is periportal, in the latter 
the glomeruli and the corticomedullary boundary contain the pigment; 
in both the cells are free. Among the rarer sites are the choroid plexus, 
the various glands of the body, and the walls of the blood-vessels. 

Pigmentation by cutaneous absorption apart from tattooing is 
problematic; it has been alleged to occur in workers in copper. 

Hematogenous Pigmentation 

This concerns the deposition of pigments derived from the hemo- 
globin, of which there are two groups, the siderous and the non-siderous. 
The chief siderous pigment is hemosiderin, which has, however, many 
modifications; the non-siderous pigments are derivatives of hematin — 
hematoidin, hemofuscin, melanin, etc. In the course of time the siderous 
pigments may lose their iron. Probably all formation and further elabora- 
tion of these pigments are the result of specific cellular activities. Two 
groups of hematogenous pigmentations may be distinguished: (1) those 
in which hemolytic agents act in the circulating blood or the asso- 
ciated organs, and (2) those in which the reductions occur locally. 

(1) To the first group belong the general hemolyses. In pernicious 
anemia and leukemia, in malaria, in severe cachexias, in occasional in- 
fectious and septic processes, in poisonings (as by pyrogallic acid, 
chlorates, arseniuretted hydrogen, by some mollusks, by pyridin and 
toluylendiamin, etc.), the hemoglobin is set free in the circulation. 
It is promptly excreted by the kidneys, and to a limited extent by the 
intestines; much is converted into bile in the liver, some little passing 
into the bile unchanged. A certain amount is reduced by the tissues 
(apparently by the liver) to the two before-mentioned series of pig- 
ments, which are then carried in the lymphatic and vascular circulation, 



102 



A TEXT-BOOK OF PATHOLOGY 



and by means of cellular carriers are deposited in various places. As 
time passes, these pigments seem to become reduced, the iron being largely 
excreted by the intestine and the remainder by the kidneys as urobilin. 
In the liver the depositions are mainly in the periphery of the lobule; 
in the spleen, in the region of the follicles, and especially in the endo- 
thelium; in the kidney the most marked collections are in and about the 
glomeruli and the tubules. In all tissues the depositions are both inter- 
cellular and intracellular; the cells may either take up pigment or have 
it deposited in them. 

Hemochromatosis. — Von Recklinghausen first described under this 
name a condition in which iron-containing pigment is deposited in the 
epithelia of the abdominal glands, especially the liver and pancreas, and 
iron-free pigment in the smooth muscle-fibers of the intestines, and the 
walls of blood-vessels and lymph-vessels, as well as in connective tissues. 
He found cirrhosis of the affected organs associated with the pigmenta- 
tion. Later a form of widespread pigmentation of the same character 
and involving the structures named, as well as other organs, and notably 
the skin, and attended with glycosuria, was described by French writers 
under the name of diabete bronze. In this condition there is pronounced 
cirrhosis of the liver and pancreas, and the diabetic association is at- 
tributed to the involvement of the latter organ. Cases without pan- 
creatic cirrhosis of a certain grade or kind are unattended with diabetes. 

Alcoholism, cachexia, and suppositious toxemias of other sorts have 
been regarded as of etiologic importance. The pigment is certainly of 
hematogenous origin, and is believed to be due to an altered metabolism 
in pigment-carrying proteins. The deposits in the cells cause degenera- 
tion and death of the latter and consequential cirrhosis. 

The appearance of organs with marked hematogenous pigmenta- 
tion varies with the variety and stage. A rusty-red color is the usual 
early appearance; later a brown, then a greenish, color may be pro- 
duced, and finally a dark blackish brown. The association of jaundice, 
which is common, alters appearances very much. 

(2) The two chief causes of local pigmentation are thrombosis and 
interstitial hemorrhage and coagulation. The pigmentations seen in 
the indurations resulting from prolonged venous stagnations and 
congestions are of analogous origin. Under these circumstances 
the hemoglobin is diffused from the blood-cells, and a portion passes 
directly into the plasmatic circulation and is carried away to be 
eliminated; soon, however, the area becomes walled off and the two 
sets of pigments are then formed within. The siderous pigments are 
most frequently seen in small lesions and at the periphery of large 
ecchymoses; the hematoidin series is most prevalent within the cystic 
contents. The pigments change in color (the color changes in a bruise 
are due to this), and finally become a brownish amorphous matter, 
which in turn disappears. Phagocytic cells take up all forms of the 
pigments (Fig. 22) and carry them to various parts of the body, espe- 
cially to the liver, hematopoietic organs, intestines, and glands; the 
depositions in them are known as pigment metastases. 



RETROGRESSIVE PROCESSES 



103 



The distinctive reactions of the various pigments are not well 
known. Of hematin and hemin it is known that they are insoluble in 
water, alcohol, and ether; slightly soluble in weak acetic and mineral 
acids; easily soluble in chloroform and in weak alkalies, from which 
solution they are precipitated on the addition of lime- or baryta-water. 




Fig. 22. — Phagocytic cells of the sputum containing blood-pigment, from a case of cardiac 
congestion of the lungs (Jakob). 

Hematoidin differs from these in being somewhat soluble in ether, but 
insoluble in weak acetic acid, and gives with strong nitric acid the 
spectral play of colors. Apart from the iron reactions little is known of 
hemosiderin. The iron is best demonstrated by its conversion into the 




Fig. 23. — Hematoidin crystals from an old hemorrhagic focus (Jakob). 

sulphid by means of ammonium sulphid, or by the Prussian-blue reac- 
tion with weak hydrochloric acid and potassium ferrocyanid (Perls' test). 

Microscopically , hematogenous pigment presents three chief appear- 
ances: small needles, rhombic crystals, and amorphous masses or 
fine balls clumped together (Fig. 23). The first two forms are very 



104 



A TEXT-BOOK OF PATHOLOGY 



rarely seen within cells, the last form commonly. The colors vary from 
a pink-red to a deep rubin, from pale yellow-green to a deep brown or 
absolute black. 

Hepatogenous Pigmentation 

Pigmentations derived from the bile are due to bilirubin (isomeric 
with hematoidin) and its oxidation product, biliverdin. Jaundice ordi- 
narily is of hepatic origin, but late observations would seem to indicate 
that bilirubin can be formed in the body without the action of the 
liver. The importance of this is not yet understood. Jaundice can 
also appear when a great hemolysis occurs, for if too much hemoglobin 
be thrown upon the liver, all the bilirubin cannot be discharged with 
the bile and is reabsorbed. 

The presence of bile or its salts in the blood occurs as a result of 
external obstruction to the bile flow, or of internal mechanicochemical 
conditions favoring abnormal retention. The bile passes into the blood 
mostly by way of the lymph-channels, but may go into the vessels 
directly, as in cases of acute yellow atrophy. The bile-salts and pig- 
ments are both in the blood in icterus and are responsible for some 
toxic effects, such as degeneration of endothelium with hemorrhage and 
depression of the central nervous system. 

The deposition of these pigments may be either in solution in the 
tissues, in granular precipitations, or in crystals (needles and rhombic 
plates). The cerebral substance alone seems never, except in the new- 
born, to be pigmented. The liver, skin, mucous membranes, the end- 
arteria and other serous membranes, and the glandular and fatty 
tissues are especially susceptible. The color is first yellow and gradually 
deepens to a deep olive, the urine presenting similar transitions. The 
lacrimal and salivary glands, the mammae, and the intestinal mucosa 
seem to be able to keep the pigment from passing out with their secre- 
tions. The ocular fluids are colored. 

The pigment in solution saturates the tissues. The granular pig- 
ments, yellow, brown, or greenish in color, may be seen in the cells or 
in the interstitial tissues; the crystals, yellow or red in color, are usually 
extracellular. The pigment displays the spectral play of colors on con- 
tact with strong nitric acid, and is turned green by weak tincture of 
iodin. 

A special form of deposition is the bilirubin infarct in the urinary 
tubules. These are seen in severe jaundice of the newborn, but may 
occur in deep icterus of adults, as in acute yellow atrophy. 

Metabolic Pigmentation 

The pigmentation derived from cellular activity may be properly 
termed "metabolic." We know isolated facts about the different forms, 
but there is little systematic fundamental knowledge. Two facts, 
however, seem clear: that these pigments are formed by migratory and 
resident pigment-building cells, which with leukocytes and plasma cells 



RETROGRESSIVE PROCESSES 



105 



accomplish the transportation and deposition of the pigments; and that 
hemoglobin is in some way or other the raw material for their manu- 
facture; some authors, however, think that protein under the influence 
of ferments produces these metabolic pigments, of which melanin is an 
example. 

The manifestations may be local or general. Among the former 
are the pigmentations of nevi and moles, of pregnancy, of the corpus 
luteum, freckles, some scars, certain skin diseases, as chloasma and 
xanthelasma, of the lesions secondary to some cutaneous parasites, 
etc. A special local type is that seen in tumors, notably in melanosar- 
comata. Lipomata and sarcomata (chloromata) may be analogously 
affected. 

Among the general pigmentations are those of Addison's disease, of 
certain severe anemias and cachexias, of tuberculosis of the peritoneum, 
intestines, and retroperitoneal glands, of abdominal neoplasms, and of 
senility. The cases associated with abdominal lesions are held to be con- 
nected with disturbances of the adrenal bodies or of the chromaffin sys- 
tem, which has been considered to have control of pigment formations. 

Odchronosis is a black pigmentation of cartilage and related tissues, 
sometimes including fibrous tissues, and on occasion associated with 
melanuria. It probably belongs with the metabolic pigmentations. 

The metabolic pigments are very varied, and a detailed discussion 
of them here would be unprofitable. They may have a high percentage 
of sulphur and may or may not contain iron. They are commonly de- 
posited in and between the cells as granules, but may be crystalline. 
They do not give a play of colors with nitric acid, and have varying 
solubility. 

NECROSIS 

Definition. — Necrosis may be defined as the death of tissues. 
The death of individual cells is termed necrobiosis; death of tissue 
en masse, usually accompanied by putrefactive changes, constitutes 
gangrene. 

Etiology. — All classes of cellular death may be brought under 
four etiological groups: 1, those due to nutritional and circulatory dis- 
turbances; 2, those due to trophic disturbances; 3, those due to poisons 
— animal, vegetable, bacterial, and inorganic; and, 4, those due to trau- 
matism, employing the term in its broadest sense. It has been at- 
tempted, without success in our opinion, to class the trophic necroses as 
identical with those due to circulatory and nutritional disturbances; 
similarly, the poisons and traumatism have been considered as acting 
only through the circulatory and nutritional paths, but it seems evident 
that in the light of our present knowledge the four groups are to a greater 
or less degree distinct. 

The various causes do not produce constant types of necrosis, 
but occasion one form in some cases, another in other cases. Promi- 
nent among these varying circumstances are the native health of the 
tissues and their vital resistance, the circulatory relations of the part 



106 



A TEXT-BOOK OF PATHOLOGY 



involved, the activity and duration of the causal agents, the age of the 
subject, the presence of other diseases, the temperature of the tissues, 
etc. It will, therefore, be better first to consider collectively the causes 
of necrosis, and subsequently detail the varieties of it. There can be 
no doubt, however, that in the direct forms of necrosis the results are 
to a marked extent individual to the agent; for example, cells killed by 
the action of acids, alkalies, and metallic salts present appearances quite 
characteristic of each. 

Circulatory Derangements. — The circulatory disturbances include 
many conditions. Acute and chronic ischemia, however produced 
— by embolism, thrombosis, arteriosclerosis and atheroma, by extra- 
arterial pressure, by cardiac weakness or by arterial spasm, as in Ray- 
naud's disease and perhaps in ergotism — are important conditions. 
Venous stagnations are responsible for many instances. Actual stasis 
due to mechanical obstructions and such poisonings as produce coagula- 
tions is a rare cause. Heat and cold act partly by circulatory disturb- 
ances. Among the general disorders of circulation and nutrition may 
be mentioned the anemias, the cachexias, senility, and certain meta- 
bolic diseases, such as diabetes. In these conditions there is much 
probability that poisoning by metabolic products plays an important 
part. 

Trophic Derangements. — Forms of necrosis due to trophic dis- 
turbances are well illustrated by bed-sores (decubitus), myelitic cystitis, 
the ulcerations seen in trigeminal neuritis, and the arthropathies. These 
forms of cell death cannot be brought under the circulatory, toxic, or 
traumatic classification. They can be explained only by the assumption 
that the biological mechanism of the cell is disturbed, and that in conse- 
quence death occurs. 

Intoxications. — The group due to poisons is very extensive and 
the particular subdivisions numerous. The toxins of bacteria furnish 
many examples of direct necrosis, and act indirectly in cases which 
seem circulatory or traumatic, though they are not really so, since these 
factors only lower the resistance of tissues, which then become suscep- 
tible to bacterial action. Experimentally the most exquisite forms of 
cell degenerations and necrosis can be produced by the injection of 
toxins or analogous substances like ricin and abrin. The alkaloids 
possess marked power in the production of necrosis. Acids, alkalies, 
metallic salts, and innumerable other chemical substances may produce 
direct necrosis, or indirect necrosis by the preliminary production of 
degenerations. The same substances often cause both circulatory and 
mechanical disturbances, which augment their direct effects. Heat and 
cold act like chemicals; heat alters the properties of proteins; cold affects 
the fluids rather than the protoplasmic substances; both also induce 
marked circulatory disturbances. 

Mechanical Agents. — The mechanical causes of necrosis are many 
and varied. Pressure per se may cause the death of cells, but is often 
aided by the circulatory disturbances which it occasions. That tension 
causes necrosis is an old surgical truth, well illustrated by the results 



RETROGRESSIVE PROCESSES 



107 



of collections of exudates below the periosteum and by the results of 
strangulations. The pressure of calculi, concretions, enteroliths, and 
exostoses may cause important necrotic processes. Circulatory dis- 
turbances often are a very active factor — indeed, many forms of trau- 
matism act solely through them. 

Inflammation, whatever its original inception, may become so ex- 
treme as to lead to necrosis. Necrosis, on the other hand, often leads 
to inflammation, the dead cells constituting the primary irritants. 

All forms of necrosis are accompanied to a greater or less extent 
by the various degenerations. In particular the cellular alterations 
are constantly present, and constitute the evidences of morbific action. 
The changes are due to disturbances of cell chemistry, among which 
enzyme action is, of course, the most important. (Reference will be 
made below to the cellular changes.) 

There are several general forms of necrosis which, however pro- 
duced, have a sufficiently distinct character to warrant separate de- 
scriptions. They are coagulation necrosis, liquefaction necrosis, casea- 
tion, fat necrosis, hemolysis, and gangrene. 

COAGULATION NECROSIS 

Definition. — This is defined as that form of death of tissue in 
which the protein suffers a change similar to or identical with coagula- 
tion. It is seen only in those tissues which are rich in proteins, and 
possibly is due to coagulation of some of these by ferments set free by 
cell necrosis. The process is partly at least a species of fibrin formation, 
and is allied to hyaline degeneration. It may be chemically distinct 
from the coagulation of inflammatory exudate, as fibrin is not always 
demonstrable. Physically the two are almost exactly the same. 

Etiology. — The causes of this condition are those above de- 
tailed for necrosis in general. Circulatory disturbances, except throm- 
bosis or infarctions, play a minor role here. Chemical irritants and 
high temperatures frequently produce it. Bacterial poisons are very 
prone to produce it, especially those elaborated by the pyogenic bacteria, 
the tubercle bacillus, and the diphtheria bacillus. About every abscess 
is found more or less coagulation necrosis; it is one of the early changes 
in tubercles and the fundamental element in the production of pseudo- 
membranes. All exudates and transudates are liable to coagulation. 

The serous and mucous membranes are most susceptible; next the 
muscular tissues (often the myocardium). 

Pathological Anatomy. — The tissue has a glazed, opaque, waxy 
appearance, and is firmer and paler than normal. In later stages the 
color becomes gray and the tissue inclines to soften. Microscopically 
it is seen that there is an exudate which has been fixed in the tissues; 
fibrin is seen (with suitable stains) in the form of granules and fibrils. 
In addition to the fibrin there is more or less homogeneous matter 
(fibrinoid) which does not react to stains like fibrin, but which is never- 
theless closely allied to that substance. The cells soon lose their elec- 



108 



A TEXT-BOOK OF PATHOLOGY 



tion for stains (Fig. 24). Early in the process the nuclei may stain faintly 
and present a homogeneous appearance; later the cell disintegrates com- 
pletely (Fig. 25). In muscles the striations disappear; and in the car- 
diac muscle the intercellular cement substance seems to be dissolved, 



^ "... 




Fig. 24. — Embolic abscess of the pancreas. The darker area in the center represents 
closely packed staphylococci, filling a blood-vessel and invading the surrounding tissues. 
The light area around this represents cellular necrosis. The peripheral darker zone shows 
abundant invasion of leukocytes. The extreme periphery of the illustration shows pan- 
creatic tissue little altered. 



for the cells often lie separated and present vacuolation and fragmenta- 
tion. Pus, leukocytes, and red blood-cells in the affected areas all suffer 
the fate of the fixed tissue. The blood-vessels at the margin of the area 
are seen to be thrombosed. In the kidneys the tubules may contain firm 
casts. 



\ 




« ■ 



I ♦ 



v « 



* • 



Fig. 25. — Coagulation necrosis of the hepatic cells in a case of puerperal eclampsia (Karg 

and Schmorl). 

Morbid Physiology. — Many chemicals cause coagulation by 
direct action. In the larger number of instances, however, it must be 
assumed that the fibrinogenetic substances which bring about the 
coagulation of the proteins are derived from the necrobiotic cells in the 
area or are carried thither by the lymphatic cells. There is consid- 



RETROGRESSIVE PROCESSES 



109 



erable evidence that bacterial products may act fibrinogenetically. It 
has been contended that coagulation necrosis is simply a species of in- 
spissation of the tissues. This is certainly not the case. 

An area of coagulation may be cast off by the process of ulcer- 
ation, may undergo liquefaction, caseation, or suppuration, may be 
encysted, and apparently may be dissolved and reabsorbed. The 
area of disease may finally be converted into scar-tissue by secondary 
regeneration. More or less complete loss of function results from 
this form of necrosis. 

LIQUEFACTION NECROSIS 

Definition. — This change consists in the death of tissue with 
colliquation. It may be divided into primary and secondary forms. 
Secondary liquefaction necrosis is the form in which other varieties of 
necrosis or degeneration are followed by liquefaction. Thus, areas of 
coagulation necrosis, cheesy necrosis, and of inflammation, gangrenous 
tissue, and tumors may become liquefied. 

Among the special forms may be mentioned vesicle formation and 
the softening of caseous tuberculous lesions. A very frequent seat of 
liquefaction necrosis is the central nervous system, where the condi- 
tions are unfavorable to coagulation, so that liquefaction here follows 
pathological conditions which would elsewhere produce coagulation. Cir- 
culatory disturbances, traumatism, and intoxications all cause soften- 
ing in the central nervous system; the peripheral nerves are much less 
susceptible. 

Pathological Anatomy. — In the early stages the tissue is softer 
than normal and very rich in fluid. Later, when the solution of the 
fibrillar tissues is advanced, the area becomes filled with a liquid of 
greater or less consistency, depending upon the tissue involved. The 
cells in the area are seen in all stages of degeneration; later, nothing but 
detritus is visible. In some instances, instead of becoming more and 
more fluid, the exudate undergoes coagulation. The color may be 
white, from the presence of an emulsion of fats; yellow, from fats and 
pigments; red and brown, from the presence of blood-pigment; and 
deeply colored when jaundice is associated. 

The process consists in the infiltration of fluid into tissues and the 
more or less complete solution of the tissue elements in it. It has been 
compared to the alterations of proteins by digestion — a reasonable de- 
duction, since the solution of the tissue or infiltrate occurs by digestive 
ferments. Should the process be of bacterial origin, the enzymes of 
the organisms are added to those of the infiltrative cells. Should 
bacteria be absent, the ferments are freed chiefly after disintegration of 
the cells. (See Autolysis.) 

Areas of liquefaction may discharge their contents, may coagulate, 
may be reabsorbed, encysted, or, in uncommon instances, organized. 



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CASEATION 

This is the crude name applied to a complex process whose product 
has a cheese-like appearance. 

The condition is most frequently seen in connection with tubercu- 
losis, although it is found in the other granulomata, and also in other 
pathological processes. The preliminary conditio sine qua non of caseation 
is coagulation necrosis. The modern view of the origin of caseation 
seems to be that it is a failure of an infiltrate to undergo complete lique- 
faction necrosis because the enzyme-bearing leukocytes are not attracted, 
and such enzymes as may be present are inhibited by the unsaturated 
fatty acids of the tubercle bacilli. Anemia of caseous areas, tuberculous 
or other kinds, plays a large part in the incomplete softening. Caseous 
matter is composed of coagulated protein and fatty matter. Second- 
ary infection brings blood-serum, which dilutes the enzyme-inhibiting 
soaps. 




Fig. 26. — Large tubercle of the lung, showing cheesy necrosis. 



The early tubercle, before the occurrence of softening, has an appear- 
ance like that of cheese, but is less homogeneous and more granular 
(Fig. 26). A form of caseation quite similar in appearance occurs in 
pneumonia, in tumors, and especially in syphilis. Soft caseation is 
usually coagulation necrosis advanced to liquefaction, together with 
fatty metamorphosis, so that the appearances are those of soft, creamy 
cheese. The liquefaction necrosis of the central nervous system may 
present similar appearances. 

Microscopically, the tissues in caseation show no cells preserving 
their staining reactions; everything is converted into debris. Around 
the affected area is usually found a zone of coagulation, of inflamma- 
tion, or both. 

Tissues that have undergone caseation may be cast off, reabsorbed, 
or encysted; resolution is not possible. Calcification is a frequent 
termination. 



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111 



FAT NECROSIS 

This term is now used to designate a peculiar type of necrosis to 
which the fatty tissues are subject, and is distinct from ordinary fatty 
metamorphosis. In human beings it is seen almost exclusively in the 
abdomen, abdominal walls, and subperitoneal fat. In nearly all in- 
stances it appears in connection with pancreatic disease — cysts, tumors, 
obstruction to the duct, and the various forms of acute pancreatitis. 
In rare instances the pancreas has not seemed especially diseased. In 
one case known to one of us of hypertrophic cirrhosis of the liver the 
omentum was affected, while the pancreas showed nothing but a moder- 
ate degree of fibrosis. 

The affected areas are white in color, usually not larger than a 
pea; they may be soft or quite gritty. Inflammatory reaction may 
or may not surround them. On microscopical examination crystals of 
the fatty acids may be seen, together with more abundant crystals of 
a combination of lime with the fatty acids. This combination, it ap- 
pears, is not a primary feature in the necrosis, suggesting that the 
fatty acids are first set free and then unite with lime-salts. In experi- 
mental work by Hildebrand, Williams, and Flexner it seems to have 
been shown that the typical condition may be the result of direct action 
of the fat-splitting ferment of the pancreatic secretion. It is certain, 
however, that in some cases of pancreatic cysts containing steapsin no 
fat necrosis has occurred. Bacteria have been supposed by some to be 
the essential agents causing the change, but this has not been demon- 
strated. 

H. Gideon Wells, after quite extensive experiments on animals, 
states that fat necrosis is merely a special form of necrosis of fat tissue, 
differing from the simple necrosis chiefly in the sharp limitation of the 
affected area, usually by a wall of leukocytes and later by connective 
tissue, and the filling of the necrosed cells by the products of fat 
splitting. 

It seems to be due to the action of one of the ferments of the pan- 
creatic juice, most probably lipase (steapsin). As this ferment cannot 
be isolated, absolute proof is wanting. It may be that the lipase causes 
the fat splitting after some other ingredient of the pancreatic secretion 
has injured the cell. 

The digestive enzyme is supposed to reach the fatty tissues of the 
abdomen by weakness of the pancreatic duct wall or pancreas capsule 
due to obstruction or inflammation. In such a condition bacteria may 
also escape and assist in the fat necrosis. Entrance of bile or intes- 
tinal contents into the pancreatic duct is said to favor the production 
of fat necrosis. 

Lipase acting on the fat cells splits up their contained fat into 
glycerin and fatty acids. Glycerin diffuses, leaving behind the fatty 
acids. The cells become necrotic and eventually the fatty acids com- 
bine with calcium salts and are precipitated, while a new growth of con- 
nective tissue encapsulates the area and diminishes its size. 



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Dissemination of fat necrosis outside of the abdominal cavity has 
been observed as early as twelve hours after intraperitoneal injection 
in animals, the route of spreading being probably by the lymphatics. 

The suggestion made at one time that bacteria might be the cause 
of fat necrosis has been entirely given up at the present time. 

Focal Necroses. — This is a condition of multiple small necroses in 
areas barely visible to the naked eye or discoverable microscopically. 
They occur in all parenchymatous organs and glands. The chief 
causes are vegetable toxins. In the small areas the nuclei first lose 
their staining reactions, the cytoplasm later. There occurs an influx of 
leukocytes, giving the appearance of an early abscess. These necroses 
are accounted for in two ways: bacteria or their products may be 
present directly in the foci, or the necroses may be due to obstruction 
of capillaries. The obstruction may be embolic or, as Pearce suggests, 
in the nature of a thrombosis due to hemolysis with collection of ery- 
throcyte debris. 

Hemolysis, or blood destruction, is a term limited to the red cells, 
and indicates destruction of the cell with dispersion of its hemoglobin. 
(The causes and other features are described under Pigmentation and 
Diseases of the Blood.) 

GANGRENE 

Definition. — Gangrene, formerly defined as the death of tissue 
en masse, is perhaps best defined as the putrefaction of areas of necrosis. 
It may be primary, when a particular bacterium produces a gangrenous 
inflammation as its direct result, as in malignant edema; or secondary, 
when saprophytic bacteria decompose an area already necrosed from 
other causes. It may be dry or moist, according to the location and 
supply of fluids. It may, furthermore, be circumscribed, progressive, or 
metastatic. 

Primary gangrene constitutes a specific affection or, rather, a number 
of specific affections. Malignant edema, infectious emphysema, and 
some forms of anthrax may be included in this group. In these condi- 
tions there is violent infective inflammation, with practically immediate 
gangrene of the affected parts. 

Secondary gangrene is more common, and the appearances are very 
varied. The essential condition is putrefaction of a necrosed area. 

Dry gangrene is usually due to vascular disturbances. As a result 
of arterial obstruction it is seen in the extremities in senility, and follow- 
ing arterial embolism or thrombosis of whatsoever nature if the collateral 
circulation be insufficient to nourish the part. Freezing may produce 
a dry form of gangrene, the vessels being blocked by thrombosis. Ergot- 
ism causes dry gangrene as a rule; the same may be said of Raynaud's 
disease. Finally, dry gangrene may result from the moist form, when 
putrefaction is slow and evaporation of the fluids occurs. The putre- 
factive processes in the dry type are not marked and may cease entirely. 
Dry gangrene is generally circumscribed and the end-result of a typical 
case is mummification. The color is usually dark, finally black; early 



RETROGRESSIVE PROCESSES 



113 



it may be yellow or brown; rarely the tissues are very pale. There is 
little toxic absorption in these cases. 

Moist gangrene presents numerous varieties. It is rarely produced 
by arterial occlusion, but is the usual result of extensive venous occlusion. 
Internal emboli, as in the pulmonary arteries or veins or mesenteric 
arteries, not infrequently cause gangrene of this form. It also occurs 
in the lungs as a result of inspirational or other pneumonias, abscess, 
neoplasms, bronchiectasis, and in diabetes. It is seen as a result of trau- 
matism and pressure in severe contusions (especially with vascular 
injuries), in intussusception and strangulation of the bowel; as a result 
of torsion in movable kidneys, spleens, or tumors. It is frequent in the 
obstructed or strangulated vermiform appendix. Extensive moist 
gangrene of the extremities or other parts is not rare in connection with 
diabetes. The mucous membranes may become gangrenous as a result 
of various infections. A particular form is noma of the mouth and geni- 
talia. It is seen as a rare condition in certain skin diseases; and is not 
unusual in severe trophic lesions, as decubitus, cystitis, mal perforans, 
etc. 

In moist gangrene the consistency of the part becomes progress- 
ively softer. There may be local or widespread emphysema. The 
color is usually dark brown, due to disorganized blood-pigment; the 
skin commonly becomes black and is covered with blebs. About the 
area there may be a zone of coagulation necrosis with vascular throm- 
bosis, or a zone of inflammatory reaction which will produce a line of 
demarcation. In some cases, especially the diabetic, neither of these 
zones is formed. 

The cells first succumb. The protoplasm and nuclei exhibit various 
evidences of degeneration, the nuclei disappearing and the cells becom- 
ing converted into granular detritus. Fat and the myelin-sheaths of 
nerve-fibers are reduced to free fat and fatty crystals. The muscle 
cells lose their striations and become fragmented; the axis-cylinders of 
nerves fibrillate. Hemorrhages into the area are common, due either 
to erosion of vessels and expulsion of their thrombi by the pressure of 
the blood-current, or to a genuine hemorrhagic condition the result of 
toxemia. Connective tissue and elastic fibers resist longer than the 
cells, but finally become liquefied. The affected area contains crystals 
of pigment, fatty acids, cholesterin, leucin, tyrosin, phosphates, and 
carbonates. Ammonia, the fatty acids, indol and skatol, sulphuretted 
hydrogen, carbonic acid and other gases, usually of pronounced odor, 
are formed. There is more or less toxic absorption from these areas. 

But two things can happen to an area of gangrene: it may progress 
and cause the death of the individual, or may become circumscribed. 
In dry gangrene and in the vascular forms of moist gangrene, limitation 
is the rule; the other moist forms tend to be progressive. In the cir- 
cumscribed form a line of demarcation is formed by inflammatory reac- 
tion, and the mass is finally cast off as a sphacelus or slough if the area be 
superficial, or encysted if the area be internal. The latter cases may be 
followed by reabsorption of the contents and calcification of the sac. 

8 



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A TEXT-BOOK OP PATHOLOGY 



GENERAL PATHOLOGY OF CELLULAR NECROSIS 

The cell as an individual element is liable to pathological processes of various 
kinds that merit brief consideration, apart from definite forms of tissue degeneration 
and necrosis. 

Etiology. — The causes of cellular degeneration and necrosis are numerous, 
including mechanical, thermal, electrical, chemical, and vital (trophic) influences of 
various kinds. It is easy to demonstrate the influence of some of these causes 
in the unicellular organisms, such as amebse, and the changes thus produced may 
also be seen under proper conditions in the cells of the animal body. 

Pathological Anatomy. — The cell as a whole may show various forms of distortion, 
or internal change. Increased irritability and mobility of the protoplasm cause the 
projection of pseudopodia, and these may be separated from the body of the cell 
as rounded particles more or less resembling the original cell. This is easily demon- 
strable in red blood-corpuscles subjected to heat. Sometimes particles are discharged 
from the cell and vacuolations (expulsion vacuoles) result. Certain influences, like 
cold and metallic salts or other poisons, cause a reduced mobility and general con- 
traction of the cell. 

ALTERATIONS IN CELL NUCLEI IN NECROSIS 

1. Karyorrhexis. 

a. Degeneration of the Cell Membrane (Chromatolysis). 

b. Budding of the Cell Membrane. 

c. Pyknosis. 

a. Degeneration of the cell membrane is a regular phenomenon of grad- 

ual physiological cell destruction, as in the ovary, testis, epithelia, 
etc. The membrane thickens (hyperehromatosis) and shows clumped 
areas. 

b. In the budding process the nucleus may be small and deeply and 

homogeneously stained and surrounded by small spherical, bud-like 
projections, or there may be very large club-like projections which 
extend to the periphery of the cell or even outside the cell. 

c. The pyknotic nucleus is smaller than normal, deeply staining and 

homogeneous in character. Contraction of the nucleus leaves a 
vacant zone about it, so that it seems to lie in a vacuole. 

2. Karyolysis. 

The nucleus undergoes a gradual solution, but its size and shape may 
still be recognized by the delimitation of the surrounding proto- 
plasm even after complete solution. 

This, in contradistinction to the various types of karyorrhexis, is 
essentially a postmortem change and occurs when dead cells are 
still surrounded by tissue fluids. 

ALTERATIONS IN THE FORM OF CELLS IN NECROSIS 

In association with pyknosis of the nucleus the cells shrink and become jagged. 
In conditions in which there is fluid surrounding necrotic cells, the cells at first swell 
and later contract. Various irregularities of shape may occur. 

Among the various forms of degenerative change in the cell preceding its necrosis 
are vacuolization, cloudy swelling, and dropsical degeneration, loss of pre-existing 
granules or granulation of previously homogeneous protoplasm, pigmentation, and 
hyaline and glycogenic change. These degenerations may affect only part of the 
cell, the surrounding protoplasm remaining healthy. In such cases the appearance 
of alien inclusions is given, and such areas of degeneration have frequently been mis- 
taken for animal parasites. Russell's fuchsin bodies are examples of this condition. 

Among the changes observed, alterations in the Altmann granules, which occur 
in many cells, are significant. These granules first become larger and more readily 



RETROGRESSIVE PROCESSES 



115 



demonstrable, their affinity for acid anilin stains increasing. These changes are 
variously ascribed to increase of acid radicals from protein cleavage in autolysis, to 
precipitation of colloids, and to condensation of colloids by pressure when the endos- 
mosis of water and solids is greater than the exosmosis of metabolic products. 
The changes are exemplified in the cellular degenerations known as cloudy swelling . 
and hydropic degeneration. 

Certain methods, such as hardening in a mixture of 2 per cent, osmic acid solu- 
tion and £5 per cent, potassium bichromate solution, staining in hot 20 per cent, 
anilin-oil acid-fuchsin solution, differentiation with alcohol, picric acid solution, are 
necessary to demonstrate the granules. In the degenerated cell even the fresh tis- 
sue or that hardened in alcohol or formol and stained with acid anilin suffices. 

Next the granules lose their characteristic arrangement; they partly dissolve 
and partly aggregate in large spherical masses which may be extruded from the cells. 

In the third stage there is an altered chemical composition evidenced by changed 
staining affinity. The granules without special preparation of the tissue may be 
stained with Weigert's fibrin method, or they may lose their staining capacity, or in 
the third place, acidophilic granules may become basophilic or the reverse. 

ALTERED KARYOKINESIS IN NECROTIC CELLS 

1. The chromosomes may become notably thickened, especially in cases in 

which injuries are inflicted on cells already dividing. 

2. Granular fragmentation and alteration of staining reaction of the chromo- 

somes. The cell itself may be vacuolated. The nuclear fragments be- 
come acidophilic. 

3. Hypochromatic Mitosis. The number of chromosomes may be reduced 

to 6 or 8 or to an uneven number, as 7 or 5. Such changes are seen in 
rapidly growing malignant tumors and in rapidly regenerating tissue acted 
upon by destructive agencies. 

4. Broken Chromosomes. Parts of chromosomes broken off from the main 

body are scattered about in the cell outside the nuclear spindle. The 
process seems to be one essentially affecting the achromatic spindle. 
Thickening, clumping, and oxyphilic change of the chromosomes are asso- 
ciated conditions. 

Such changes have been found in cells unfavorably influenced after division 
was under way. 

5. Asymmetrical Mitosis. The daughter stars may have an unequal number 

of chromosomes and thus be of unequal size. 
This has been found in carcinomata, sarcomata, adenomata, and regeneration 
of the epidermis. 

6. Hyperchromatic and Multiple Mitosis. 

The number of chromosomes may be excessive and there may be pluripolar 
mitosis, the number of centrosomes and corresponding spindles being 4-6, 
8, and even 20. 

POSTMORTEM ALTERATIONS 

Certain changes take place after death which may suggest in their appearances 
antemortem disease. It is, therefore, necessary to recognize these in postmortem 
examinations. The most striking change is the rigidity or rigor mortis, which is due 
to a coagulation of the muscle albumin or myosin, probably by reason of the lactic 
acid present. This occurs at different intervals, according to the cause and nature 
of death. Sometimes, as in deaths after electrical discharges, it occurs almost in- 
stantaneously; more commonly its beginning is delayed for some hours. It appears 
early in cases dying with active muscle metabolism, and late in wasting diseases. 
After twenty-four or forty-eight hours the rigidity disappears. Occasionally irregular 
postmortem contractions of the muscles take place, and distortions or even move- 
ments are thus produced. 



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Circulatory Phenomena. — As is noted elsewhere (see Congestion), the blood- 
vessels, especially the arteries, contract after death, and drive the blood into the 
capillaries and veins. It is then more or less free to sink to dependent parts through 
the influence of gravity, and in consequence the lower parts of the organs and of the 
body in general are congested. This is particularly marked in the lungs, but occurs 
in practically all organs. The blood may remain entirely within the blood-vessels, 
but not rarely the coloring-matter diffuses itself through the tissues and causes 
pigmented areas (livores mortis) that may suggest antemortem bruises. 

The blood in the heart and other vessels tends to coagulate, though in some 
cases this is long delayed and remains imperfect. Usually dark red clots are found 
in the cavities of the heart and in the large vessels. Yellowish fibrinous clots are 
less likely to be postmortem, but more often occur in cases in which death has taken 
a lingering form. 

Postmortem Degeneration of Tissues. — Some time after death the tissues may 
become macerated and putrefactive changes may occur. To a large extent these 
are due to invasion of micro-organisms. It has been found that during the terminal 
stages of disease various forms of infection (especially micrococcic) occur. This 
terminal infection is often the immediate cause of death, and it is also concerned in 
the postmortem change in the tissues. Histologically, a striking peculiarity of such 
postmortem change is the absence of evidences of reaction (cellular infiltration and 
proliferation), such as characterize the response of living tissues to irritation. 

Postmortem softening of the mucous membranes may be due to the action of 
the secretions. This is especially marked in the stomach, where it is common to 
observe a macerated condition of the mucosa of the posterior wall. In this case the 
gastric juice is the direct cause of the alteration in the mucous membrane. 

Autolysis. — After death, either local or general, tissues tend to soften, the 
process being due to intracellular enzymes in the absence of bacteria. The 
activity of these ferments is held in check during life by the antiferment action of 
blood-plasma. All inhibitive agencies being removed by death, favoring factors 
appear in the shape of a slightly acid reaction due to overneutralization of tissue 
alkalinity by acids formed in fermentation and putrefaction. The intracellular 
enzyme is now freed and digests the cell. This is essentially what occurs in the 
resorption of pathological processes during life. All cellular enzymes are not identical. 
The most conspicuous cell ferment is that contained in the wandering leukocytes 
which acts as a solvent in inflammatory exudates. 



CHAPTER V 



INFLAMMATION AND REGENERATION 
INFLAMMATION 

Definition. — Inflammation is the local reaction caused by agents 
that have produced tissue injury. The essential element in this reaction 
is fluid and cellular exudation and the attraction to the place of injury 
of wandering cells. A less essential but almost invariable feature is 
local hyperemia, while the processes of repair or regeneration usually 
accompany, but are not strictly a part of, inflammation. By reason of 
the fact that the term "inflammation" was originally a clinical one and 
designated all the results of local injury, that is, damage, defensive 
processes, and repair, and further, by reason of the fact that injury and 
repair naturally go hand in hand in living tissues, it has always been a 
matter of difficulty for pathologists to determine what part of the proc- 
esses occurring in an area of inflammation constitute its essence, and 
what part represents results or consequences. In the present ^tate of 
knowledge we recognize and can distinctly separate two sets of phe- 
nomena following local injury, the first being reactive and defensive ; the 
second, reparative. The latter, while intimately interwoven with the 
former, do not differ from regenerative processes that are known to 
occur without inflammation. Viewed in this light the term "inflamma- 
tion" is restricted to the defensive processes that follow injury, while 
the repair of damage is a natural sequel manifesting the vital capacity 
of tissues to restore themselves. 

There are certain other consequences of inflammation that are some- 
times included among its essential phenomena. Thus, certain pathol- 
ogists insist that inflammation is general, not merely local; that the whole 
body participates in certain ways. There can be no doubt that the irri- 
tants causing inflammation as well as products of tissue distruction do 
gain access to the circulation to some extent, and thus occasion general 
results throughout the body, and it is also true that widespread co- 
operation may be induced through the action of the nervous system. 
These are results or sequels of inflammation, but not an essential part 
of the condition. When the local defensive mechanisms occurring in 
inflammation (let us assume, of bacterial origin) are inadequate, the 
micro-organisms may gain access to the general circulation and general 
"infection'' result; when products of tissue destruction similarly 
escape into the general circulation an "intoxication" results. Neither 
of these is an essential part of inflammation, but rather the evidence 
that this process has been inadequate to fulfil its purposes. Such 
cooperation of the whole body as may be induced through the nervous 

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A TEXT-BOOK OF PATHOLOGY 



system is reactive and is similar to that which must of necessity attend 
any local disease. It, too, is a consequence, but not an essential part, of 
inflammation. 

For purposes of description, however, it is better to include in the 
chapter on inflammation the regenerative processes that accompany 
it, and also some account of the general reactions of the whole body. 
Regeneration independent of inflammation, or with but slight evidences 
of preceding inflammation, will be separately considered later. 

Historical. — The earliest conception of inflammation was that of a specific 
entity. Subsequently various theories were offered in explanation of the several 
phenomena or symptoms. First, the blood-vessels were supposed to be influenced 
through the nervous system (vascular theories). Next, it was taught that the inflam- 
matory irritant excites proliferative changes in the tissues (thus giving rise to round 
cells), and that this stimulation of the cellular activity invites more blood to the 
part (hence the hyperemia). This was the cellular and attraction theory of Virchow. 
Others, notably Cohnheim, described the emigration of leukocytes from the blood- 
vessels, and held this to be the essential feature of inflammation. This emigration 
was first described by Dutrochet (1824), Waller (1842), and Strieker; but Cohnheim 
was the first to systematize the emigration theory. According to Virchow, the first 
step is a formative stimulation of the cells; according to Cohnheim, degeneration of 
the vessels leading to emigration; according to Weigert, at least in many cases, the 
first step is necrosis of the parenchymatous cells. Metchnikoff and his students 
would elevate phagocytosis to the position of the essential feature of inflammation, 
but the prevailing opinion is that reactive tissue changes and enzyme activity are 
equally important, both within and without the cell. 

Galen and his followers defined inflammation by giving the cardinal 
symptoms: heat (color), redness (rubor), pain (dolor), and swelling 
(tumor). To these may be added altered function (functio loesa). 

Phenomena of Inflammation in Vascular Tissues. — These may 
be well studied in the mesentery or tongue of a frog. When the mesen- 
tery is exposed and spread under a microscope and a localized area in- 
jured, the first visible effect is a very temporary contraction of the 
arteries, which may disappear before the examination can be made. 
It is followed by dilatation of the arteries, and then of the capillaries 
and veins. The tissue becomes distinctly more vascular than normal 
as capillaries in which there had been only plasma or a few corpuscles 
become distended with blood, and, therefore, more distinct. The blood- 
current is at first more rapid than normal, then slower, and may finally 
stop entirely (stasis), especially in the capillaries and veins in the center 
of the inflamed area. Notable changes are seen in the circulating cor- 
puscles. It will be recalled that under normal conditions the corpuscles 
circulate in the middle of the vascular stream, leaving a clear plas- 
matic zone adjacent to the vessel wall; in this zone may be seen leuko- 
cytes traveling somewhat more slowly than the central corpuscular 
stream. As the current becomes slower the leukocytes in the plasmatic 
zone increase in number and stick to the vessel walls, at first here and 
there, holding on uncertainly, but finally becoming more firmly attached 
and arranging themselves in a continuous row. In the capillaries clumps 
of leukocytes frequently alternate with masses of red corpuscles, or of 



INFLAMMATION AND REGENERATION 



119 



red and white corpuscles in their customary proportion. Next, it may 
be observed that the leukocytes are passing through the walls of the 
capillaries and veins and spreading in the outside tissues. At first a bud- 
like projection pushes itself through the vessel wall, then more and more 
follows until the whole leukocyte has escaped into the tissue space 
outside the vessel. At the same time a certain number of red cor- 
puscles pass through the capillary walls, and altered plasma escapes and 
infiltrates the tissues. Some of the leukocytes enter the lymph-channels 
and thus return to the circulation; others suffer degeneration and de- 
struction locally. 

In the perivascular tissue the emigrated leukocytes are found in 
tissue spaces and tend to accumulate where the injury is greatest. If 
there be a large area of destruction, these cells surround it. The leuko- 
cytes soon exhibit their phagocytic power by enclosing bacteria, fragments 
of dead cells, and debris. The enclosed parts are dissolved by the 
intracellular ferments and are soon unrecognizable. Some of the 
phagocytes are themselves destroyed in this attempt to remove invading 
bacteria and degenerated cells; and becoming, in turn, degenerated, break 
down into a debris upon which other phagocytes feed. There appear 
within the cellular exudate also large mononuclear phagocytic cells with 
large palely staining nuclei, the so-called macrophages. These take up 
all kinds of debris or even whole leukocytes and red blood-cells. Their 
origin and functions will be considered later. 

While this is going on, reparative processes appear in the shape of 
round newly formed connective-tissue cells which alter their form to 
spindle or irregular contour, and finally produce fibrillar projections. 
These are fibroblasts, the principal regenerative cells. 

In structures in which there are parenchymatous (archiblastic) 
cells the latter undergo various degenerative changes, such as cloudy 
swelling, edema, mucous degeneration, fatty degeneration, or even 
necrosis. Less frequently proliferation of the parenchymatous cells 
takes place. 

. Every case of inflammation does not present all these phenomena, nor 
is the subsequent fate of the exudate and altered cells always the same. 

Phenomena of Inflammation in Avascular Tissues. — Some of 
the processes of inflammation have been best elucidated by experi- 
mental inflammation of the cornea. It will be recalled that this struc- 
ture is composed of. layers of parallel fibers, the direction of the fibers 
in one layer being at angles to that of the fibers of adjacent layers. 
Anastomosing lymph-channels occupy the spaces between the fibers 
and layers, but there are no blood-vessels. A very slight injury of the 
cornea may be followed by no other result than slight swelling of the 
corneal corpuscles around the point of injury and subsequently multi- 
plication of these cells to repair the damage. This slight change cannot 
be readily demonstrated. Usually there is seen around the injured spot 
a hazy zone which is composed of masses of leukocytes that have been 
attracted to the center of irritation. These escape from the hyperemic 
conjunctival vessels at the periphery of the cornea. The alteration 



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A TEXT-BOOK OF PATHOLOGY 



(dilatation, degeneration of the walls) of these vessels may be due in 
part to reflex nervous influences, and in part to the direct action of toxic 
substances generated at the site of the primary corneal injury and dif- 
fused to the surrounding tissues. 

The corneal corpuscles themselves swell, undergo nuclear division, 
and to some extent perhaps become free (phagocytic) cells. In more 
intense grades of inflammation the local degeneration of the corneal 
corpuscles causes a visible defect (erosion, ulcer), and the surround- 
ing zone of leukocytic invasion is pronounced. In cases of marked 
corneal inflammation new blood-vessels are later formed at the sides 
of the cornea, and pushed into its previously avascular structure; the 
subsequent phenomena are practically the same as those found in in- 
flammation of vascular tissues. 

In the case of inflammation of the heart-valves no migration of 
leukocytes to the diseased focus occurs in the early stages. The endo- 
thelial cells at the point of injury (near the free edge of the valve) swell 
and present nuclear division and also more or less degenerative change; 
the tissues at the base of the leaflets become hyperemic and some 
emigration of leukocytes occurs in this situation. Thus, as in the case 
of the cornea, cellular destruction and proliferation occur at one place 
(the point of injury), while the vascular phenomena and emigration of 
leukocytes are found at some distance. In both cases there may event- 
ually be an ingrowth of loops of capillary blood-vessels from the vascu- 
lar periphery into the avascular structure, and then local emigration of 
leukocytes from these capillaries may take place. 

The phenomena must now be separately considered. 

1. Changes in the Vessels. — The first effect of irritation may be 
momentary contraction of the arteries; but this is rarely observed. 
Usually the arteries dilate at once, and dilatation of the capillaries 
and veins promptly follows. This is at first a regular or uniform dis- 
tention, but shortly becomes irregular, causing inequality of caliber and 
tortuosity. The cause of this dilatation was formerly located in the 
nervous system, and undoubtedly nervous influences do play a part 
in some cases at least, but the more important cause is probably some 
degeneration of the vessel walls. The primary dilatation may be due 
to the direct effects of the toxic agent causing the inflammation or to 
products of cell degeneration it has occasioned. It may be purely func- 
tional at first, but later is surely degenerative. The microscope does 
not reveal this, but some of the phenomena connected with exudation 
and the circulation of the blood show that there is some lesion of the 
vessel walls. There are certain visible changes in the vessels, such as 
swelling of the endothelial cells and increase of the intercellular sub- 
stance, and some undoubted though invisible changes, such as increased 
adhesiveness of the endothelial cells. The last-mentioned condition 
and the swelling of the endothelial cells which thus encroach upon the 
lumen of the vessels are conditions that, together with the dilatation of 
the blood-vessels, occasion slowing of the blood-current and adhesion of 
the leukocytes to the vessel wall. 



INFLAMMATION AND REGENERATION 



121 



In the later stages of inflammation karyokinetic changes and con- 
sequent multiplication of the endothelial cells of the capillaries are ob- 
served. The new-formed endothelial cells are utilized in the production 
of new blood-vessels. (See Granulation Tissue.) 

Influence of the Nervous System. — It is likely that the nervous system 
through its vasomotor mechanism plays an important role both centrally 
and peripherally in the vascular and exudative phenomena of inflam- 
mation. Dilatation of the vessels may be favored by weakness of the 
constrictors or stimulation of the dilators. This is illustrated by the 
severe inflammations resulting from trivial causes in paralytic parts, and 
by the occurrence of sympathetic inflammation in one eye following 
disease of the other. In the latter instance the trophic nerves are also 
concerned. 

2. Exudation. — As the blood-current grows slower the leukocytes 
in the plasmatic zone of the blood-stream increase in number and cling 
to the wall of the vessel. This is partly a mechanical result of the 




Fig. 27. — Inflammation of the mesentery, showing overfilling of the blood-vessels, with 
emigration of leukocytes and diapedesis of red corpuscles (Ziegler). 

slower rate of the blood-current, and partly the result of the adhesiveness 
of the vessel walls and projection of the endothelial cells. Possibly the 
attractive (chemotactic) influence of the agents causing the inflammation 
may play some part by drawing the leukocytes to the walls of the 
vessels (see below). Finally, the leukocytes pass through the vessel 
walls between the endothelial cells and collect on the outside of the 
blood-vessel, whence they more slowly migrate through the tissue 
(Fig. 27). The passage of the leukocytes through the vessel wall can be 
studied in the mesentery of the frog. At first a bud-like projection pushes 
itself through the wall between the endothelial cells, then more and 
more of the corpuscle follows until the whole cell has escaped. When 
outside the blood-vessel the cell creeps through the tissues in the inter- 
cellular spaces, often elongating itself in narrow places to a linear form, 
and again swelling to its normal rounded form where fluid exudate has 
widened the spaces. This emigration of leukocytes occurs to a slight 
extent normally, but is abnormal in degree in inflammation. Cohn- 



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A TEXT-BOOK OF PATHOLOGY 



heim ascribed it to disease of the vessels — increased permeability — the 
leukocytes being purely passive. Later observation indicates that the 
chief role in this excessive emigration must be assigned to the stimulated 
ameboid movements of the leukocytes. Degeneration of the vessel 
walls, especially swelling and softening of the cement substance between 
the endothelial cells, and the pressure of the blood, aid, but only to a 
minor extent. The cause of this active ameboid motion and tendency to 
emigration has recently been found to be an attractive force peculiar to 
the causes of inflammation. Stahl, and later Pfeffer, found that certain 
substances exert an attractive or repellent force upon low forms of 
vegetable and animal life, upon spores of plants, and upon bacteria. 
To this force the name chemotaxis has been given, and the terms positive 
and negative chemotaxis are used to designate the attraction and the 
repulsion respectively. The irritant substances which directly cause 
inflammation are positively chemotactic in action; and in cases in which 
mechanical injury causes inflammation, such substances first result 
from mechanical destruction of cells and then incite the subsequent 
phenomena of inflammation. The leukocytes that emigrate under the 
influence of a chemotactic agent are almost exclusively the polymorpho- 
nuclear forms, and these constitute the majority of the cells of an 
inflammatory exudate in its earlier stages. They are not, however, the 
only forms of leukocytes found in an inflammatory area. Frequently 
the first to appear are the eosinophiles. Sometimes these cells are 
very abundant in the inflamed part. In somewhat later stages lympho- 
cytes also emigrate, and as the polynuclear forms disappear the lympho- 
cytes become more and more predominant. In part these doubtless 
emigrate from the blood-vessels, but the greater number is derived 
from the lymph-channels and regional lymphoid collections, for such 
collections are exceedingly widespread throughout various tissues and 
organs. The lymphocytes are prone to occur in groups, which has led 
some authorities to attribute their presence to hyperplasia of existing 
lymphoid collections, and to some extent to the attraction exerted on the 
lymphoid cells of the neighboring lymph-spaces toward the existing 
lymph-nodes in the affected area. While the tendency is to group 
together, they also increase among the growing fibroblasts, and, as 
said above, crowd out the polymorphonuclears. Plasma-cells 1 and mast- 
cells are also found, but as the significance of these is still doubtful, 

1 Plasma-cells. — The cell described under this term by Unna is a small cell whose 
protoplasm stains a violet blue with methylene-blue. There are no distinct granules, 
though sometimes the protoplasm is slightly granular. The granules have some relation 
to those in the lymphocyte. This cell is one of the so-called lymphocyte series. The 
nucleus is usually eccentrically placed and surrounded by dark masses of chromatin. 
The cell varies in size from that of the small lymphocyte to that of the large mononuclear 
leukocyte. Karyokinesis has been observed in a few cases. The plasma-cell is probably 
an altered lymphocyte which has escaped from the blood-vessels. Some hold that it is a 
form of connective-tissue cell and that it is concerned in regeneration of connective tissue. 
This is unproved and unlikely. The plasma-cell is found in inflammatory exudates of all 
sorts and in the lesions of the specific infectious diseases — tuberculosis, leprosy, syphilis, 
etc. 

The plasma-cell of Waldeyer is different from that above described. It is identical 
with the mast-cell of Ehrlich. This is a cell containing large basophilic granules. (See 
Diseases of the Blood.) It occurs in inflammatory processes of a chronic character and in 
various tumors and degenerative lesions. Its significance and nature are uncertain. 



INFLAMMATION AND REGENERATION 



123 



separate reference will be made to them below. The plasma-eell un- 
doubtedly plays an important role in some cases, as the inflammatory 
exudate may consist almost wholly of this type of cell. 

The microscopical appearance of the tissues after emigration of 
the leukocytes is characteristic. The capillaries are dilated and ob- 
scured by a mantle of exuded white corpuscles, and the tissue around 
swollen by fluid and infiltrated with migratory leukocytes. The sub- 
sequent distribution and appearance of the leukocyte depends very 
much upon the character of the inflammation and of the tissues in which 
it occurs. 

The changes going on within the cell consist of fatty, cloudy, albu- 
minoid, or dropsical degeneration of organ cells, while hyaline or mucoid 
metamorphosis is seen in connective-tissue cells. 

The cellular character of the exudate varies somewhat with the tissue 
involved and the nature of the irritant. For example, in the pyogenic 
infections at the height of the condition one sees almost exclusively 
polynuclears. In tuberculous inflammations lymphocytes predominate; 
while in pneumonia, polynuclears and epithelial cells are in greatest 
numbers. 

Diapedesis of Red Corpuscles. — Finally, a certain number of red 
corpuscles escape from the capillaries by diapedesis. This is a purely 
passive process so far as the red corpuscles are concerned, being due to 
pressure of the blood. It is particularly marked when stasis and con- 
sequent intravascular thrombosis has occurred. In very intense in- 
flammation accidental hemorrhage per rhexin may add to the blood in 
an exudate. 

Role and Fate of the Leukocytes. — The most essential element in the 
defense against the injurious agents that cause inflammation is the emi- 
grated polymorphonuclear leukocyte. This cell possesses a marked 
capacity to swallow or ingest bacteria or other foreign bodies, which 
has given the process the name phagocytosis, and the cell exercising this 
function the name phagocyte. When bacteria (especially pyogenic 
micrococci) or small particles of insoluble material, such as carmin or 
carbon, are introduced into the tissues or into serous cavities, polymor- 
phonuclear leukocytes speedily gather about and incorporate the foreign 
bodies in their protoplasm. So far as bacteria are concerned, some 
preliminary action is exerted on them by the blood-serum of the fluid 
exudate (see below). This is demonstrated by the fact that the poly- 
morphonuclear cells will take up larger numbers of micrococci from a 
suspension in serum than from one in normal salt solution. The sub- 
stances which act to prepare the micro-organisms are termed opsonins 
(see p. 258). Possibly precipitins and agglutinins also aid in some 
measure. After their ingestion the micro-organisms are either digested 
within the phagocytic leukocyte and thus disappear, or the phagocyte 
with its contents enters lymphatic channels and reaches the regional 
lymphatic nodes. Thus the micro-organisms are disposed of and re- 
moved from the center of infection as speedily as possible. Insoluble 
foreign bodies and products of tissue destruction (fatty globules and 



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A TEXT-BOOK OF PATHOLOGY 



detritus) are also taken up by the phagocytic leukocytes and dissolved 
or removed to the neighboring lymphatic nodes. In this combat with 
the foreign invaders a certain number of the leukocytes perish and may 
be found in various stages of disintegration. Some of them are ingested 
by other polymorphonuclear leukocytes, but in the later stages of inflam- 
mation they are found enclosed in other phagocytic cells of large mono- 
nuclear type, which will be described presently. 

The various processes described bring about a removal of the micro- 
organisms or other causes of inflammation, and at the same time a steady 
diminution of the number of polymorphonuclear leukocytes at the 
point of inflammation. The lymphocytes now begin to be more con- 
spicuous in number. Their role, however, is less definitely determined. 
Some of them seem to undergo a swelling and transformation into the 
large mononuclear phagocytic cells that will be described below. It 
was formerly held that some of them become engaged in the process of 
reproduction of tissue, being first converted into formative or fibroblastic 
cells. This view is probably erroneous, the evidence being that neither 
the ordinary lymphocyte nor the variety known as plasma-cell has such 
a function. 

The eosinophile leukocytes may sometimes be abundant in inflam- 
matory exudates, and it has been suggested that they are active in 
throwing out bacteriolytic substances. Further proof of this assump- 
tion must be forthcoming. 

In all of these processes in which the emigrating leukocytes are 
concerned soluble substances and enzymes are essential. These will be 
referred to after the liquid exudation has been discussed. 

Large mononuclear -phagocytic cells become conspicuous in the area 
of inflammation after the primary leukocytic phase begins to subside, 
and in certain inflammations they are so almost from the beginning. 
These cells are of variable size, always large, and sometimes of giant 
proportions. The rather large pale nucleus and the phagocytic prop- 
erty of the cells are their distinguishing characteristics. The general 
term "macrophages" may be used to designate them, though it indi- 
cates no special derivation. The origin, indeed, is still uncertain, but 
among the possible sources of derivation are the lymphocytes, the 
endothelium of lymph-glands and channels, blood-vessel endothelium, 
and various wandering tissue-cells. It is not probable that the fixed 
tissue-cells of the locality give origin to them. The macrophages are 
specially concerned in taking up leukocytes and fragments of cellular 
destruction. Sometimes a number of polymorphonuclear phagocytes, 
with their own inclusions, all more or less degenerated, are found within 
a macrophage, and there may be, in addition, red corpuscles and debris 
of other cells. The complete digestion of these contents may occur in 
part in the area of inflammation, but some of the macrophages, like some 
of the polymorphonuclear phagocytes, perhaps find their way to regional 
lymphatic nodes; and similar cells primarily make their appearance in 
the lymphatic nodes when the polymorphonuclear phagocytes invade 
these structures. 



IXFL.UIiLA.TION AND REGENERATION 



125 



Giant-cells, containing multiple nuclei, are found in certain forms of 
protracted or chronic inflammation. They will be described later. 

Exudation of Liquids. — Coincidentally with leukocytic emigration 
there is exudation of more or less altered blood-plasma. The amount of 
liquid exudation and the character of the exudation -v ary with the 
nature and condition of the tissue affected and the character of the 
irritant. In loose cellular tissues and in inflammation of membranes 
lining cavities large quantities of liquid are poured out of the vessels, 
while the reverse is seen in denser parts. Some intense irritants occasion 
free exudation, while others, by their very intensity or peculiar charac- 
ters, at once destroy the tissues, and exudation is comparatively slight. 

The exudate is richer in albumin and more coagulable than dropsical 
fluid, which is a further indication that the blood-vessels are more per- 
meable in inflammation than in health or mere congestion. It is prob- 
able, moreover, that the capillary walls act in a secretory manner, as 
do the walls of the lymphatic channels. This would in some measure 
explain the difference between inflammatory exudate and dropsical 
liquids. The accumulation of exudate in the tissue may be so abundant 
that the term inflammatory edema is justified. In such cases, as in all 
inflammations to a less extent, the cause of the retention of liquid in the 
inflammatory area is in part a reduction of tissue tone or elasticity which 
prevents the movement of the fluid toward the efferent lymph-channels. 
Thrombosis of lymphatic vessels, induration of surrounding tissues, 
and edematous and cellular swelling of regional lymph-nodes are also 
causes for the retention of liquid exudate in an inflamed area. 

After its exudation the fluid may undergo coagulation by inter- 
action with fibrin ferment derived from disintegrated leukocytes, 
with formation of fibrin and consequent solidification of the inflamed 
area. When inflammations affect mucous membranes there is usually 
active stimulation of the epithelial cells and outpouring of mucus, which 
materially alters the exudate. 

The exudate plays an important role in inflammation. Among its 
uses may be mentioned that it serves as a diluent of noxious bodies, 
that it brings from the blood substances that aid in destroying the irri- 
tants, and that it may carry similar substances derived from the leuko- 
cytes, either secretions or products of their degeneration. Occasionally 
it has the unfavorable action of carrying away and thus spreading 
throughout the system the causes (bacteria, for example) or products 
of the inflammation. In the case of fibrinous inflammation, the fibrin 
serves to strengthen the limiting wall by which an inflamed area is sur- 
rounded. The highly nutritious character of the liquid is doubtless of 
importance in the proliferative processes that are presently to be 
described. 

3. Chemical Processes Involved in Inflammation. — Many of the 
features of inflammation have been made clearer by recent studies of 
certain chemical relations of the cellular and fluid exudates. It has been 
found that the leukocytes carry in their substance an active proteolytic 
enzyme which acts best in an alkaline medium. This enzyme doubtless 



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A TEXT-BOOK OF PATHOLOGY 



operates to dissolve bacteria and other albuminous bodies ingested by the 
phagocytic leukocyte. When this enzyme is liberated by disintegration 
of emigrated leukocytes it is capable of attacking the tissues and soften- 
ing them or digesting them, but this result is prevented when sufficient 
fluid exudate is present, because the latter contains an anti-enzyme 
which destroys or in some manner neutralizes it. This is, perhaps, the 
same anti-enzyme which is present in normal blood-serum, and which is 
capable of restraining the action of trypsin. Should leukocytic exuda- 
tion become excessively abundant, owing, for example, to virulent highly 
chemotactic micro-organisms, or should the physical nature of the tis- 
sues prevent an adequate fluid exudate, the amount of leukocytic en- 
zyme liberated becomes disproportionate to the amount of anti-enzyme, 
and there results a proteolytic softening of the tissues and exudate with 
resulting pus formation. This disproportion of enzyme and anti- 
enzyme, therefore, determines the occurrence of suppurative instead 
of non-suppurative inflammation. 

In the later stages of inflammation, when the leukocytes have largely 
disappeared and the mononuclear phagocytes are in evidence, a differ- 
ent proteolytic enzyme is found. This has been studied especially in 
tuberculous tissues with abundant epithelioid cells. This enzyme acts 
best in an acid medium, and is probably active in the destruction of 
leukocytes and various cellular remnants ingested by the macrophages, 
from which it is derived. Opie has suggested the names leukoprotease 
and lymphoprotease for the enzymes derived from the leukocytes and 
mononuclear cells respectively. 

Other chemical processes besides those mentioned are involved in 
inflammation. The first effect of the action of inflammatory irritants, 
whether merely mechanical or micro-organismal, is cellular destruction, 
and consequent liberation of substances that are chemotactic and to 
some extent toxic. There follows the exudation of leukocytes and liquid. 
Chemical combination between fibrin ferment derived from disintegration 
of leukocytes or other cells and the liquid exudate causes fibrin for- 
mation, and thus some solidification of the inflammatory exudate. 
Later, this fibrin, together with the more or less degenerated cells in 
the area of inflammation, may be digested by the action of the leuko- 
protease before described, and perhaps by the action of similar if not 
identical enzymes derived from the blood-serum. 

Micro-organisms call forth special chemical defenses. As has been 
related, the micro-organisms are in large part ingested by phagocytic 
leukocytes and are in some way destroyed within these. It has been 
shown that substances called opsonins are important in preparing micro- 
organisms for this ingestion by phagocytes, and probably bactericidal 
substances derived from the blood-serum in the inflammatory exudate, 
as well as precipitins and agglutinins, are also important agents in the 
preparation for phagocytic destruction of micro-organisms. It has, 
indeed, been shown that living and virulent organisms may be taken up 
by phagocytes, but their preliminary destruction or devitalization seems 
to be the rule. Some of the micro-organisms, doubtless, are destroyed 



INFLAMMATION AND REGENERATION 



127 




----- 



and carried off into the lymphatic channels without the aid of phago- 
cytes. It is asserted by some observers that besides the enzymes of 
blood- and tissue-cells described above, there is in these cells a separate 
and extractable substance which can destroy bacteria. Its office in 
inflammation is not understood. 

4. Proliferative Changes. — Sooner or later in an inflamed area, 
and especially at the periphery, there are evidences of cellular pro- 
liferation which occasions the ap- 
pearance in the tissue of round 
cells closely resembling lymphocytes 
or mononuclear leukocytes. They 
differ, however, in being somewhat 
larger, in having a larger and paler 
nucleus, which is round or oval, 
and in their frequently exhibiting 
evidences of karyokinesis. These 
cells are direct derivatives of the 
fixed connective-tissue cells and of 
endothelium lining lymph-spaces. 
The parent cells first undergo en- 
largement by swelling of their pro- 
toplasm, then mitosis of the nuclei 
and cell division follow. The new- 
formed round connective-tissue cells 
may in part become wandering cells 
and more or less phagocytic, but the 
greater number remain fixed and 
become elongated or polymorphous 
in shape, produce intercellular sub- 
stance, and thus assume a purely 
regenerative role. These are desig- 
nated fibroblastic cells. (See Re- 
generation.) 

At the stage under considera- 
tion the cellular elements of in- 
flamed tissue consist of emigrated 
leukocytes, now reduced to a small 
number, many lymphocytes, large 
mononuclear leukocytes, and round 
connective-tissue cells. The ap- 
pearance is characteristic of the more advanced stages of acute in- 
flammation and of chronic inflammation. It is termed round-cell infil- 
tration (Fig. 28). 

Virchow held proliferative changes to be the essential feature in 
inflammation, and believed that all round cells are concerned in this 
process; Cohnheim denied that proliferation is the important feature 
of inflammation, and ascribed to emigration the essential role. Later, 
it was held that the proliferative changes are not, in reality, a part of 





Fig. 28. — Acute appendicitis, with ex- 
tensive round-cell infiltration of all of the 
coats of the appendix. 



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A TEXT-BOOK OF PATHOLOGY 



inflammation, but rather regenerative and for the purpose of repairing 
the tissue injuries after inflammation (Fig. 29). At the present time 
many regard as factors in inflammation both emigration and prolifera- 
tion, whether the latter in any individual case is due to direct stimula- 
tion of the cells, or is secondary to destructive changes, or is merely the 
result of increase of nutrition from the inflammatory congestion. It 
is conjectured by some that under chemotactic influences the cell 
contents of fixed cells are incited to movements terminating in karyo- 
kinesis, just as the whole cell is influenced in the case of movable cells. 
The proliferation of the fixed connective-tissue cells may be an early 
process, but does not usually occur until some time after the exudative 
changes have taken place. The new-formed cells have at first the 
characters above described, but later they become irregular and many 
of them spindle shaped (formative cells or fibroblasts). In chronic 




Pig. 29.— New blood-vessels and fibroblastic cells in a beginning adhesion of the pericardial 

layers. 

inflammations, especially such as surround foreign bodies, giant-cells 
are found. These have distinct phagocytic functions. 

Giant-cells may be divided into: (a) Foreign body giant-cells with 
peripherally located nuclei and a homogeneous, somewhat degenerated 
center. They arise in degenerating tissue, probably by coalescence of 
multiplying endothelial or large plasma-cells. Some authors think they 
are due to direct nuclear division or nuclear division too rapid for the 
protoplasm to keep pace with it. (b) Myeloplaxes are giant-cells with 
uniformly distributed nuclei and a homogeneous protoplasm such as 
are seen in the bone-marrow and tumors, (c) Parenchymatous giant- 
cells are found in tumors, in regenerating interstitial tissues, or in the 
parenchyma of organs. The nuclei may be irregularly distributed, but 
are commonly connected by narrow isthmuses of chromatin. They 
arise by rapid nuclear division. 

Granulation Tissue. — When the proliferative changes are active, 
new blood-vessels, formed by multiplication and lateral outgrowth of 



INFLAMMATION AND REGENERATION 



129 



the endothelium of the pre-existing vessels, are a conspicuous feature. 
These, surrounded by the various forms of round cells above described, 
and sometimes giant-cells, constitute granulation tissue. (See also Repair 
of Wounds and Regeneration.) Such granulation tissue is especially 
conspicuous on the floor of ulcers, and exemplifies the regenerative proc- 
esses which follow immediately in the wake of the frank inflammatory 
reaction. 

Proliferative Changes in the Parenchymatous Cells. — Swelling and, 
later, mitosis may occur in the early stages of inflammation, but are 
of slight extent. In certain chronic inflammations also, such as some 
forms of cirrhosis of the liver, proliferation of parenchymatous cells 
may be observed. In the latter instance the process is rather definitely of 
regenerative character. The changes in the earlier stages of inflamma- 
tion are more truly inflammatory, though the new-formed cells, unlike 
some of the proliferative connective-tissue cells, do not migrate or take 
on phagocytic action. 

5. Degenerative Changes in the Tissues. — The first attack of in- 
flammatory irritants is made upon cells of fixed tissues, that is, upon 
cells of the parenchyma of an organ, upon the connective-tissue cells, 
or upon the walls of blood-vessels. The emigration of leukocytes and 
their combat with the irritants follows. In the case of bacteria which 
contain within their substance positively chemotactic bodies, it would 
seem probable that there is an immediate activity of these bodies; but 
various considerations make it more probable that even in the case of 
bacteria the first effect is exercised upon fixed cells. In the case of 
mechanical irritants damage or complete destruction of cells is the 
first step toward inflammation. Weigert, Neumann, and others hold 
that the "primary effect" in inflammation is always such tissue injury, 
which, in turn, excites exudation and, later, proliferation. The demon- 
stration that tissue degenerations liberate positively chemotactic sub- 
stances explains how the phenomena of inflammation are brought about. 
The degenerative changes may be merely physiological (some form of 
altered functional activity), or there may be structural alterations, 
such as cloudy swelling, mucoid degeneration, liquefaction, fatty change, 
coagulation, or other forms of necrosis. The nature of the degeneration 
depends largely upon the severity of the irritation. Very powerful 
irritants cause necrosis at once, and not inflammation. It is the irri- 
tants which disorder, but do not entirely destroy, cells that are especially 
apt to excite inflammation. The cellular degenerations now under dis- 
cussion are entirely different in significance from the more conspicuous 
secondary cellular degenerations considered below. The primary degen- 
erations occasioned by the first attack of the irritant are often incon- 
spicuous and inferential rather than demonstrable. 

Secondary Cellular Degenerations. — When inflammations attack 
tissues containing epithelia or other parenchymatous cells the latter 
often suffer secondary degenerative changes, cloudy swelling, fatty 
or mucoid degeneration, and total necrosis. These secondary cellular 
changes may serve to spread and intensify the original inflammation, 

9 



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A TEXT-BOOK OF PATHOLOGY 



and are, moreover, especially harmful to the functional activity of the 
diseased organ or tissue. The cause of these degenerations may be 
the same toxic agent which initiated the whole process or, on the other 
hand, the pressure of exudates and the circulatory disturbances incident 
to the inflammation. 

Etiology. — Irritation by mechanical, chemical, thermal, or infec- 
tious agents causes inflammation when it is severe enough to dis- 
turb the vitality of the tissue and not sufficient to cause extensive 
necrosis at once. When the irritant is brought to bear upon the tissues 
directly, there is probably, first, cell degeneration, followed by vas- 
cular disturbances and emigration. Micro-organisms may act by first 
destroying the cells, or may liberate from their substance some poison 
(protein) which is irritant and chemotactic. Disturbances of circu- 
lation, innervation, or metabolism may so alter cellular processes as to 
occasion the liberation of irritating and chemotactic products. 

In the experience of surgeons bacteria stand out conspicuously as 
the almost invariable cause of "inflammation." This term, however, 
is used in a clinical rather than a true pathological sense. The proc- 
esses concerned in the healing of uninfected wounds and in other 
cases of injury unaccompanied by infection are just as truly inflam- 
matory. It must be recognized that non-bacterial injuries to tissues 
liberate substances by cell destruction which are capable of producing 
the phenomena of inflammation. Among the causes of inflammation 
in this pathological sense must be included certain endogenous proc- 
esses, notably of circulation, innervation, and metabolism, which cause 
local cellular degeneration, followed by exudative and reparative phe- 
nomena. 

Special Forms of Inflammation. — Various classifications may 
be used in describing forms or types of inflammation. The most 
natural is that which follows the anatomical changes. Thus we may 
distinguish (1) exudative inflammation, or the form in which the fluid 
and cellular exudation from the blood-vessels is the predominating 
element in the pathological process; (2) parenchymatous or degenerative 
inflammation, or the form in which destruction of the parenchyma cells 
is the leading feature; and (3) productive inflammation, in which prolif- 
eration is the striking characteristic. The nature of the cause, as well 
as the resistance of the organism or of the affected part, determine the 
particular form in a given case. 

A number of subvarieties may be described, but it must always 
be remembered that inflammation is essentially the same in all cases. 
The three processes — exudation, degeneration, and proliferation — are 
present in greater or less degree in all forms, although in some cases one 
feature, in other cases another, may be most conspicuous. 

Types of Inflammation. — 1. Edematous or serous inflamma- 
tion is characterized by a copious exudation of fluid with compara- 
tively little cellular matter, as in edema of the larynx, serous effusions 
in the serous sacs, etc. The local forms of edematous or serous inflam- 
mation are usually expressions of intensely irritant causes; the serous 



INFLAMMATION AND REGENERATION 



131 



inflammations of serous cavities, however, are not necessarily of this 
severe grade. Indeed, in many cases serous inflammation may be a mild, 
subacute or chronic, process, which may subside gradually, leaving the 
serous membranes slightly thickened or adherent. This adhesion is 
due to the fact that fibrin collects upon the serous surface during the 
acute stage, the fluid remaining free in the sac. The fluid is removed 
by absorption; the fibrin, by digestion. Lasting adhesions remain when 
proliferative changes are firmly established before the digestive processes 
can complete their work of removing the fibrin deposits. The fluid in 
inflammatory exudations differs from dropsical fluid in containing more 
albumin, leukocytes, and fibrin factors. 

2. Fibrinous Inflammation. — The plasmatic and cellular exudate 
may form a fibrinous membrane on free surfaces or a network within 
the tissues; this is termed "fibrinous inflammation" because the most 
conspicuous physical change is the excess of coagulum. 

In purely fibrinous inflammations of serous surfaces there is a whit- 
ish or yellowish-white deposit of variable thickness, which is more or 
less adherent to the underlying surface. When removed, there may be 
seen beneath it a pronounced injection of the blood-vessels and rough- 
ness and rawness of the surface. This is due to beginning granulations. 
(See Repair of Wounds.) Microscopically, the fibrinous deposit con- 
sists of an irregularly arranged mass of fibrillar, granular, or homo- 
geneous fibrin, with leukocytes and endothelial cells (more or less 
degenerated) enclosed in the deposit. The fibrin may be found in star- 
like formations made up of a more or less degenerated central leukocytic 
mass and radiating threads of fibrin extending from it in every direc- 
tion. This may be significant of the liberation of fibrin ferment from the 
degenerating cells and consequent formation of fibrin about this as a 
center. Some authorities believe that fibrinous inflammation can never 
occur independently of destruction of fixed cells. In other words, they 
doubt the possibility of fibrin formation from purely exudative elements. 
Some experimenters have, however, described fibrinous inflammations 
of serous surfaces with an unbroken lining of endothelial cells under 
the fibrinous deposit, and have concluded that the fibrin is wholly exu- 
dative. Others regard the lining cells as cells of lymph-spaces, and not 
the original surface cells; and consequently conclude that cellular destruc- 
tion always plays a part in the fibrin formation. Fibrinous inflamma- 
tion in serous sacs is often associated with serous exudation, and the 
term serofibrinous is applied. In other cases (especially in peritoneal 
inflammations) the exudate is likely to become purulent — fibrino purulent 
inflammation. 

Inflammations of the serous membranes are nearly always more or 
less fibrinous. 

3. Pseudomembranous or diphtheritic inflammation differs from the 
last in having associated with the coagulation of the exudate decided 
coagulation necrosis of the cells of the part inflamed. The difference is 
one of degree rather than of kind, and is largely dependent upon the 
character of the tissue in which the inflammation occurs. Diph- 



132 



A TEXT-BOOK OF PATHOLOGY 



theritic inflammation occurs especially in the pharynx and larynx, where 
it occasions pseudomembranes (Fig. 30). This is most frequently due 
to the specific bacillus of the disease called diphtheria; but diphtheritic 
inflammation may result from a variety of severe irritants, such as other 
bacteria, superheated steam, and chemical agents. The diphtheritic 
membrane consists of a network of fibrin or of homogeneous or granu- 
lar fibrin masses enclosing degenerated epithelial cells and emigrated 
leukocytes. Sometimes it is quite superficial, involving only the surface 
layer of epithelium ; at other times the whole depth of the mucous mem- 
brane is implicated. The former 
are sometimes called croupous 
and the latter diphtheritic false 
membranes. These terms, how- 
ever, are ill-defined and objec- 
tionable. The use of the terms 
fibrinous and pseudomevibranous, 
omitting croupous and diphthe- 
ritic as unnecessary, if for no 
other reason, is good practice. 
In any event it must be ob- 
served that the term " diphthe- 
ritic " as used in this place refers 
to a type of fibrinous inflamma- 
tion rather than to a process 
due only to the diphtheria bacil- 
lus. This organism is the most 
frequent cause of such inflammation, but other agents, as before 
noted, occasion the same type of inflammatory lesion. 

4. Suppurative inflammation is characterized by unusual abun- 
dance of emigrated leukocytes and by the tendency to liquefaction. 
Bacteria are most frequently the cause; but it has been shown experi- 
mentally that croton oil, calomel, turpentine, and other substances are 
capable of producing suppuration. Of the bacteria, the commonest are 
the so-called pyogenic staphylococci and streptococci; but numerous 
forms, not commonly pyogenic, may occasionally prove so. Such are 
the bacillus of typhoid fever, the gonococcus, the Bacillus coli, and others. 

The implantation of bacteria of suppuration at the point of disease 
may take place directly through wounds, or somewhat indirectly through 
the circulation, the micro-organisms having gained access to the system 
through small abrasions in the mucous membranes or skin. Some 
local injury may then serve to determine the suppurative inflammation 
at a given place. 

Recent studies ascribe to chemotaxis the important role in the 
action of bacteria in inflammation and suppuration. Either the prod- 
ucts of the bacteria or substances derived from their own protoplasm 
(endogenous substances) exercise a powerful chemotactic influence, and 
thus occasion the massing of emigrated leukocytes (Fig. 31). The 
preponderance of cellular over liquid exudation and the consequent excess 




Fig. 30. — Pseudomembranous inflamma- 
tion of the uvula: a, a, masses of micrococci; 
b, b, necrotic cells; c, c, round-cell infiltration; 
d, d, fibrin network (Ziegler). 



INFLAMMATION AND REGENERATION 



133 



of leukoprotease over anti-enzyme prevent fibrin formation, or cause a 
solution of fibrin already formed and a liquefaction of degenerated tissue 
elements and cells. The sequence of events is as follows: bacteria 
directly implanted in the tissue or carried to the capillaries in the blood- 
stream first cause local cellular changes (degeneration or necrosis) ; then 
congestion and exudation of leukocytes and plasma occur around this 
focus; next more or less fibrin formation results from the exudation, and 
finally, after more and more leukocytic emigration, softening of the whole 
area completes the formation of pus. The essence of suppurative in- 
flammation is the excessive emigration of leukocytes, the softening of 
the tissues, and the failure of the fluid exudate to coagulate and form 
fibrin. The excessive leukocytic invasion is chargeable to inordinate 
chemotaxis due to the micro- 
organismal or other causes of the 
inflammation or to their products. 

Pus consists of a liquid part, 
the liquor puris, a modified blood- 
plasma, which differs from ordi- 
nary plasma in being less coagu- 
lable and in containing notable 
quantities of albumose (peptone) ; 
and a corpuscular part, consisting 
chiefly of polymorphonuclear leu- 
kocytes more or less degenerated. 
The leukocytes are chiefly poly- 
morphonuclear and filled with 
neutrophilic granules. Neverthe- 
less it is not possible to identify 
these pus-cells absolutely. They 
often contain globules of glyco- 
gen and fat. Some proliferated connective-tissue cells or wandering 
cells may be added from the neighboring tissue, but these constitute 
but a minority of the whole number. The pus-cells present a distinctly 
granular protoplasm and fragmented nuclei. 

Abscess. — When circumscribed suppuration occurs in the substance 
of a tissue or organ, the lesion is called an abscess. This consists of a 
collection of pus which usually has a creamy yellow color, but may 
be variously altered by subsequent changes. The abscess grows by 
further liquefactive changes in the surrounding tissues because of the 
attraction of leukocytes with their ferments from the hyperemic vessels 
in the peripheral structures. Around the abscess the tissues present an 
indurated zone or wall in which the proliferative changes and fibrin 
formation described as part of inflammation are conspicuous features. 
There are numerous round cells, differing from emigrated leukocytes 
and often showing mitotic figures in the nuclei, and there are new 
blood-vessels and beginning organization. (See Regeneration.) Fibrin 
in the form of interlacing threads or in masses, the product of plasmatic 
exudate and of coagulation necrosis, adds to the embankment. In 




Fig. 31. — Embolic abscess in the myocar- 
dium, showing accumulation of large numbers 
of leukocytes (Karg and Schmorl). 



134 



A TEXT-BOOK OF PATHOLOGY 



slowly forming abscesses the surrounding wall of condensed tissue is 
often quite firm. This restraining wall was formerly erroneously regarded 
as a pus-producing membrane, and, therefore, called the pyogenic mem- 
brane. As a matter of fact, on the contrary, it represents the inflam- 
matory changes at the periphery of a suppurating area where the 
actively chemotaetic effects of the pyogenic agent are sufficiently re- 
duced in activity that the liquefication characteristic of pus formation 
is minimized in favor of coagulation and formative processes. 

Abscesses tend to soften the surrounding tissues in the direction of 
least resistance, and thus to break on the surface, discharging their 
contents by sinuous tracts or sinuses. This discharge not only evacuates 
the pus, but reduces pressure and permits a renewed flow of fresh blood 
through the so-called pyogenic membrane, bringing with it the anti- 
enzymes and bacterial antibodies of the serum. Sometimes, the pus of 
an abscess becomes inspissated by absorption of the liquid part, and the 
residue undergoes various degenerative changes, such as mucous, 
fatty, or calcareous. At the same time the surrounding membrane 
may advance to complete organization, and thus encapsulates the 
abscess. 

Phlegmonous Inflammation. — Suppurative inflammation may have 
a less definitely circumscribed character than that seen in abscesses. 
It may take the form of a purulent infiltration in which the tissues are 
extensively infiltrated with emigrated leukocytes and more or less soft- 
ened by liquef active processes, or by abundance of fluid exudate that 
does not coagulate. In other cases a nearer approach to the conditions 
seen in abscesses is observed when the purulent process spreads along 
planes of tissue or neighboring foci coalesce to form a diffuse suppura- 
tive condition. To this the terms phlegmon and phlegmonous inflam- 
mation are applied. 

Ulcer. — Suppurative inflammation with erosion of areas of the skin 
or mucous surfaces occasions ulcers. The floor of an ulcer has the same 
histological construction as the wall of an abscess. In it may be seen small 
red points or granulations, which consist of loops of capillary blood- 
vessels surrounded by round cells. (The histology of granulation 
tissue is more minutely described under Regeneration.) 

The clinical features of ulcers vary widely. Sometimes rapid de- 
struction of the tissues causes large and spreading ulcers, called phage- 
denic. Others extend in one direction while healing in other parts, and 
are called serpiginous. The granulations may be too rapid in growth, 
forming red fungous masses (proud flesh) which fill up the ulcer. In 
other cases the ulcer remains dry and indolent, showing little tendency to 
heal. 

Some ulcers are not primarily of inflammatory origin. For example, 
the round or peptic ulcer of the stomach is formed by digestion, through 
the action of the gastric juice, of a part of the stomach which has be- 
come lowered in vitality or possibly necrotic. Similarly, the beginning 
change in the perforating ulcer of the foot in tabes and in decubitus (bed- 
sores and other forms of pressure ulceration) is not inflammatory, but, 



INFLAMMATION AND REGENERATION 



135 



rather, necrotic. Secondarily, however, the necrotic tissues in these 
cases become active irritants and occasion true inflammatory ulceration. 

Suppurative inflammations of serous membranes lining closed sacs 
cause collections of pus in the cavities. The pus usually contains more 
or less fibrin, and there is a fibrinopurulent exudate on the serous 
surface. 

Suppurative inflammation of the skin and subcutaneous tissues may 
be localized or diffuse. Of the localized type, there are various pustules, 
furuncles or boils, and carbuncles. 

A furuncle is a suppurative and necrotic inflammation beginning 
in one of the sweat-glands, sebaceous glands, or hair-follicles. A car- 
buncle is a more extensive but similar process beginning in several of the 
glands or hair-follicles simultaneously, and causing considerable necrosis 
or gangrene of the skin and subcutaneous tissue. 

5. Hemorrhagic Inflammation. — More or less diapedesis of red 
corpuscles generally occurs in inflammation; but sometimes the irritat- 
ing cause falls with such peculiar force on the blood-vessels or the 
general condition of the patient (cancer, tuberculosis, hemophilia, 
scurvy) is such that the exudate is unusually rich in red corpuscles. 
Certain micro-organisms (organisms of hemorrhagic septicemia) more or 
less regularly cause hemorrhagic inflammation. Intravascular throm- 
bosis and obstruction of capillaries with masses of micro-organisms play 
an important part in causing the hemorrhagic exudation. These are 
always serious inflammations, and are to be distinguished from ordinary 
inflammations in which accidental hemorrhage occurs. Hemorrhagic 
inflammation, in a pathological sense, may be an early stage of other 
forms, particularly of the fibrinous variety of the lungs. There is 
severe congestion, diapedesis, and transudation of plasma, which almost 
at once make fibrin. This hemorrhagic state is transient and is not to 
be compared with the continued outpouring of blood in the hemorrhagic 
infections. The cause of the last is bacterial toxins acting upon vessel 
walls, decreasing their resistance. The effect is greatest where they are 
naturally thin, in a condition of stasis or already affected by local or 
general disease (syphilis). 

6. Catarrhal Inflammation. — This term is used to designate inflam- 
mations of mucous membranes. The character of the inflammation de- 
pends to a large extent upon the individuality of the mucous membrane 
affected, differing greatly in the nose, throat, stomach, bowel, etc. 
There is always considerable congestion of the mucosa, and generally a 
great deal of serous exudation, which is discharged from the surface as 
a rule, but is to some extent retained in the tissue, causing edematous 
swelling. This is especially marked when the submucosa is considerably 
implicated. The epithelial cells of the surface suffer degeneration 
(mucous or fatty) and necrosis, and are discharged with the serous 
exudate; they may be recognized as goblet-cells (mucous), or as granu- 
lar cells (fatty), or as fragmented necrotic structures. Coincidently 
with the serous exudation, and in greater measure after the latter has 
become less marked, leukocytes escape from the blood-vessels or emi- 



136 



A TEXT-BOOK OF PATHOLOGY 



grate from their resting-places in the submueosa and make their way to 
the surface between the epithelial cells (Fig. 32). At this stage also 
mucus becomes a more or less pronounced feature in the exudate. 
There is little fibrin formation in catarrhal inflammation, since the 
exudate moves toward the surface and escapes. The features of this 
form are the superficial exudation and desquamation after degeneration. 
When fibrin appears this catarrhal form becomes pseudomembranous. 

When in great abundance (as in some nasal catarrhs) the process 
may be a purulent or suppurative one; more frequently there is suffi- 
cient mucus to require the term mucopurulent. Superficial erosions of 
the epithelium and hemorrhages are frequently met with. 

When catarrhal inflammations are chronic, there is usually consider- 
able productive inflammation, with consequent thickening, and later, 
when the new fibrous tissue contracts, there may be uniform thinning 



>pr @ r .. : '^ S H= 




Fig. 32. — Acute bronchial catarrh, showing the escape of leukocytes from the submucous 
tissue between the epithelial lining cells (Thoma). 

of the mucosa or irregularly distributed areas of hyperplasia intermixed 
with areas of thinning. In some cases, however, progressive atrophy of 
the mucosa occurs without previous productive changes. This is espe- 
cially marked in the bowel, where, doubtless, constant distention plays 
an important part. When the contractions of the fibrous tissue are 
irregular, the mucosa between the fibrous areas may be elevated, espe- 
cially if there is at the same time proliferation of the surface epithelium 
and the glandular elements in the mucosa. In such cases a granular 
surface or polypoid elevations result. These are common in the stom- 
ach and the bowels. 

7. Parenchymatous or Degenerative Inflammation. — This term may 
be applied to certain inflammations, such as forms of nephritis in which 
degeneration (cloudy, fatty, etc.) of the parenchyma cells is more con- 
spicuous than the exudative processes. The changes in the parenchyma 



INFLAMMATION AND REGENERATION 



137 



in such cases are often secondary to the inflammation; in other cases 
they are precedent. Strictly speaking, the parenchymatous changes are 
not essentially a part of the inflammation, but in those cases in which 
much degeneration of parenchymatous cells accompanies inflammations 
the term "parenchymatous inflammation" is convenient and expressive. 

8. Necrotic or gangrenous inflammations depend for their occur- 
rence upon the severity of the irritation or the state of the general 
system. 

9. Productive Inflammation. — In this form the proliferative changes 
predominate over exudation and degeneration. This may be due 
to the nature of the etiological factor, to peculiarities in the tissue reac- 
tion, or local conditions affecting the removal of the irritant. In all 
cases in which inflammation for any of the above reasons becomes 
chronic the proliferative changes in the affected tissues become more or 
less predominating. Some degree of primary tissue destruction appears 
to be essential to the productive process, which, therefore, must be 
regarded as always reactive or regenerative. 

It is desirable to differentiate between (a) productive processes as 
the last stage of acute inflammation, (b) the newly formed connective 
tissue as the result of acute inflammation, and (c) the progressive pro- 
duction of fibrous tissue as the result of continued irritation. The lines 
between the three are not sharp. The repair of serous membrane in- 
flammation may be a simple thickening of the layer itself, but if granu- 
lations attach two or more areas together, we have adhesions which are in 
excess and probably not necessary for the healing of the original defect. 
Thus, again, in cicatrices we have nature's expression of excessive pro- 
duction for repair. When the cause of the inflammation ceases the 
productive changes usually cease, unless the tissue already made acts 
as a foreign body and continues as a mechanical irritant. If it cease, we 
have a finished reparative process as the result of inflammation. Should 
the irritant continue its action, there is continued response as expressed 
in the infectious granulomata and chronic fibroses. The last are really 
chronic inflammations. 

Repair of Wounds. — Productive inflammation is well illustrated 
in the healing of wounds. If the lips of a clean, incised wound are drawn 
together at once and kept closely apposed, rapid healing occurs, which 
is called healing by immediate union. In these cases a microscopical ex- 
amination shows slight exudation from the surfaces of the wound and 
proliferated connective-tissue cells. The epithelial continuity is restored 
by proliferation of the old epithelial cells. Should apposition be less 
immediate or less accurate, the amount of exudation is greater. If the 
wounded surfaces are examined twenty-four hours after the injury, they 
are found red and swollen and soon they become glazed in appearance. 
The microscopical features here are the same as in the case of healing by 
immediate union, excepting the amount of exudation is greater. Healing 
proceeds in the same way, but more slowly, and is called healing by first 
intention. In neither case is there great congestion. If the wound be 
irritated by foreign bodies or kept exposed, there will be seen on the sur- 



138 



A TEXT-BOOK OF PATHOLOGY 



faces, after two or three days, small red elevations, known as granula- 
tions, which consist of loops of new-formed capillaries covered by emi- 
grated and new-formed round cells, and sometimes (after longer inter- 
vals of time) giant-cells (Fig. 33). The surface may be covered with 
considerable pus. The proliferated round cells gradually elongate and 
form new fibrous tissue (see Regeneration), which afterward contracts, 
forming cicatrices or scars. The epithelial continuity is re-established 
by multiplication of the old epithelial cells at the edges of the wound. 
This form of healing is called healing by second intention or healing by 
granulations. 

The formation of adhesions following inflammation of the serous 
surfaces occurs in much the same way as wounds heal. The primary 
exudation is largely fibrin- 
ous and causes agglutina- 

tion of neighboring sur- r 5~^%K"^^^J^^< 

faces. Subsequently the _-• ■ ' - : 

proliferative connect ive-tis- r 
sue cells, having become • ^ 

actively wandering cells, \' '// . ' 

penetrate this fibrinous exu- t . •■ 




Fig. 33. — Loops of blood- 
vessels in granulation tissue 
(Thiersch). 





Fig. 34. — Adhesive pericarditis, showing fibrin 
deposit, with new blood-vessels extending upward 
into it. 



date, as do new-formed blood-vessels (Fig. 34). Thus a union of vas- 
cular channels is effected between the adjacent inflamed surfaces, and 
organization follows. 

Precisely similar changes occur in the tissues surrounding a foreign body, as a 
piece of sponge or around a portion of dead tissue. In these cases the exudative 
and proliferated cells tend to penetrate into the foreign mass, as occurs also in the 
organization of thrombi. There is in these cases a greater tendency to the formation 
of giant-cells than in ordinary granulations. If the foreign mass can be softened 
and absorbed, this gradually occurs, and later merely a scar will remain; if it cannot 
be absorbed, connective tissue eventually encloses or encapsulates it. 

General Fibrosis. — A tendency to widespread productive inflam- 
mation is noted in certain individuals. This affects the blood-vessels 
especially (general arteriocapillary fibrosis, general angiosclerosis), and 



INFLAMMATION AND REGENERATION 



139 



also the liver (cirrhosis of the liver), the kidneys (interstitial nephritis), 
and other organs (Fig. 35). Some form of degeneration or necrosis of the 
parenchymatous cells is doubtless the preliminary stage in all of these 
cases. First the endothelia or the muscle cells are affected in the cases 
of blood-vessels; the hepatic cells in case of the liver; the epithelia 
of the tubules and glomeruli in case of the kidney, etc. The resulting 
fibrosis is, however, out of all proportion to any demonstrable change 
of parenchyma. In some cases it is evident that the fibrosis is merely 
a compensatory regeneration to replace degenerated parenchyma and 
that the process is not primarily inflammatory, although some of the his- 
tological changes are akin to inflammation. It is asserted that the cause 
of this degeneration of parenchyma cells may sometimes be repeated 
protein intoxication. (See Anaphylaxis.) 




Fig. 35. — Chronic interstitial nephritis: great increase of connective tissue around the 
glomeruli, renal iubules, and blood-vessels; from a case of arteriocapillary fibrosis. 

Productive inflammation may effect other tissues than the fibrous 
connective tissues. Reference has already been made to epithelial 
proliferation in the healing of wounds. Similar epithelial processes of 
greater activity or duration may lead to warty growths of the skin or 
polypoid outgrowths on the mucous membranes. In pharyngeal ca- 
tarrhs considerable proliferation of the adenoid tissues is not unusual. 
So also thickening of cartilages, bones, or the periosteum is not an un- 
usual result of inflammation of these structures. 

Pathological Physiology. — Inflammation represents increased and 
altered activity of tissues as a result of irritation; its primary object is 
the removal of the irritant. It is a pathological state per se, but considered 
from the point of view of its result (the removal or confinement of the 
irritant and the resulting tissue destruction) inflammation is essentially 
conservative and useful. In this process no new forces or activities are 



140 



A TEXT-BOOK OF PATHOLOGY 



involved: the phenomena are all observed in normal tissues, though to 
a less degree and in more orderly behavior. The liquid and cellular 
exudation has its prototype in the formation of lymph and in the normal 
wandering cells of the tissues; the increased vascularity is the result of 
increased demand, and is abnormal in degree only; the cellular destruc- 
tion is an accentuation of the ordinary death of cells resulting from wear 
and tear, though the form of the cell destruction is more violent and 
probably different; the postinflammatory regeneration is effected by 
karyokinetic multiplication of cells, as in normal tissues. 

In the destruction and removal of the irritant, phagocytosis (q. v.) 
is important; it is accomplished by the leukocytes, by endothelial 
cells, the wandering connective-tissue cells, and giant-cells. 

Though a local process, inflammation often has widespread results. 
The causes of the inflammation gain access to the blood via the lymph- 
vessels and regional nodes before a wall of fibrin and leukocytes has been 
built up around the inflamed locality. When once the local tissue reac- 
tion has developed and the lymph-nodes are prepared, further dis- 
semination is halted. The primary invasion of the blood-stream may 
be advantageous in stimulating the antibodies of the body, which can 
then be carried to the focus of infection in the blood-plasma. The 
products of tissue change (primary cellular necrosis, degeneration of 
the emigrated leukocytes, softening of the tissue and coagulated 
exudate) entering the blood may occasion fever and other evidences of 
toxemia. 

The functional activity of a part the seat of inflammation is often 
increased, though somewhat altered. An inflamed gland may pro- 
duce an excessive but abnormal secretion. In other cases functional 
activity is lessened; chronic inflammations almost certainly lessen 
functional power. Secondary parenchymatous changes, by altering 
organic action, may be highly injurious to the whole organism. 

Resolution after Inflammation. — In cases of trivial exudation the 
emigrated leukocytes may re-enter the blood-current through the 
lymphatics. The liquid exudate is similarly disposed of, while the pro- 
liferated connective-tissue cells remain in loco or become wandering cells. 
When the exudate is more abundant, the liquid elements may be re- 
moved in the same way, but the cells first undergo degenerative soft- 
ening and are reduced to the form of an emulsion, which is gradually 
absorbed. In purulent inflammations the pus may be discharged 
through external openings or into cavities of the body or may become 
inspissated. (See Purulent Inflammation.) The degenerated paren- 
chyma in inflammation may recover if the degeneration is not severe, 
or may be softened and removed. Phagocytic cells play a prominent 
part in the removal of broken-down cellular remains, pigment masses, 
and the like. 

The reparative changes in inflammation may be so slight as to lead 
to no discoverable lesion after the process is completed; but when large 
damage has been done there is apt to be a permanent scar or some other 
productive lesion. 



INFLAMMATION AND REGENERATION 



141 



Specific Inflammations or Infectious Qranulomata. — Tubercu- 
losis. — Structure and Evolution of the Tubercle. — When the tubercle bacil- 
lus is received into any tissue or organ, its first effect, according to the 
investigations of Baumgarten, is to stimulate or irritate the fixed con- 
nective-tissue elements and endothelial cells and cause a proliferation of 
round cells, which resemble in their abundance of protoplasm the epi- 
thelial cells, and are, therefore, known as epithelioid cells. These have 
usually a single nucleus, of rather clear vesicular appearance, not deeply 
staining, and a relatively large amount of protoplasm. They may be 
produced in greater or less abundance, as the first reactive change of 
the tissues to the irritation of the tubercle bacilli. They represent 
primarily the cellular reaction on the part of the endothelial and fixed 
tissue cells, and later assume a fibroblastic character. Next there 
follows an infiltration with leukocytes from the surrounding blood- 
vessels or lymphoid collections common to all tissues, and the focus of 
irritation thus becomes surrounded 
with numerous small round cells, 
mostly mononuclear, with darkly 
staining nucleus and a small proto- 

plasmic body (Fig. 36). In more ^S^^j^j^^ r " 
acutely formed lesions polymorpho- 
nuclear leukocytes are more abun- 
dant. This leukocytic infiltration 
represents the reaction of the vas- jl 
cular system to the tuberculous irri- / 
tation or infection. The number of " 

small round cells varies greatlv in *k\ 7< A K^'Ji'-^M^°^ ; 'f^'- ^ilV 
different instances. Sometimes, as ^^:A^0M^^B^^ 
in certain tubercles of lymphatic 1"^' 
glands, they may be relatively few, \J'-H vS* | j \ 8 ffm%'* 

while the epithelioid cells are present %d i | Wfift 

in abundance. In other cases the ^. „„ v , 

, , • l i i Fig. 36. — Miliary tubercles in the liver, 

leukocytes are SO quickly attracted showing abundant round cells in the per- 

and in such numbers that the tu- Jg"™ 1 P arts - epithelioid and giant-cells 
bercle seems composed of these cells 

alone, no epithelioid cells appearing in view. These tubercles are known 
as the "lymphoid." In the later stages the round cells may disappear 
by degeneration, exposing the previously hidden epithelioid cells. 

At the stage of the tubercle when it is composed mainly of epithe- 
lioid and lymphoid cells it appears to the naked eye as a grayish, some- 
what translucent, pearly body. It is avascular, no tendency toward for- 
mation of new blood-vessels being apparent. In the further evolution 
of the lesion degenerative changes take place. These are hyaline de- 
generation, coagulation necrosis, fatty change, and eventually a trans- 
formation into cheesy material, the so-called caseous necrosis. These 
changes result from the specific action of the tubercle bacillus, though 
in part also from the avascular condition of the tissue. Avascu- 
larity alone, however, is not the cause of caseous necrosis. One of the 




142 



A TEXT-BOOK OF PATHOLOGY 



first changes noted is a granular change in the cell protoplasm which 
lessens the affinity of the cell protoplasm and of the nucleus for ordinary 
stains. There may be seen among the cells of the tubercle here and there 
individuals which show this beginning necrosis. These are usually 
grouped in the center of the tubercle, though at times also at different 
points. The outlines of these cells become less distinct and they are 
progressively less deeply stained, until with advanced necrosis the 
cell is broken down into particles or debris (Fig. 37). In the early 
stages of necrosis the epithelioid cells tend to form giant-cells either by 
coalescence of neighboring epithelioid cells or by division of the nucleus 
without division of the cell body. This is the Langhans giant-cell 
with its nuclei arranged about the periphery. The giant-cell is not char- 
acteristic of tuberculosis, as it may be found in many of the specific 
inflammations and also in foci of chronic irritation due to foreign bodies, 



arsis' 




Fig. 37. — Large tubercle of the lung, showing cheesy necrosis in the center; the epithelioid 
and giant-cells around the cheesy center are more or less degenerated. 



as well as in tumors. In no condition, however, are they so abundant or 
so conspicuous as in tuberculosis. In some cases they may not be seen 
in the tubercles at any stage. In other cases they are very numerous. 
The giant-cell falls an early victim to the advancing necrosis. Perhaps, 
in fact, the formation of the giant-cell is an evidence of beginning necro- 
sis and the division of nuclei without division of the cell is an evidence 
of the degenerative change. As necrosis of the cell advances the proto- 
plasm becomes granular and opaque, and eventually breaks down com- 
pletely. This change usually occurs at the opposite side of the cell from 
that in which the nuclei are gathered ; or in cases in which the nuclei are 
near the periphery of the cell the necrotic changes begin in the center. 
Finally, a tubercle undergoes almost complete necrosis and is trans- 
formed into a cheesy mass, the surrounding connective tissue perhaps 
still showing proliferative changes which may eventually cause encap- 



INFLAMMATION AND REGENERATION 



143 



sulation of the tubercle. Calcification may ensue in the cheesy mass 
and thus lead to permanent arrest of activity in the nodule. 

The foreign body tubercle, that due to pieces of silk, hairs, etc., usu- 
ally under the skin, differs from the specific kind in failing to undergo 
caseation, and in the prominence of connective-tissue new growth with 
some giant-cells. Tubercles arising from acid-fast organisms not the 
true tubercle bacillus are almost exactly like the specific tubercle and 
must be differentiated by bacteriological methods (Fig. 38). 

In the growth of tuberculosis the normal tissue elements of the 
part effected are pushed aside, or may be softened and destroyed by 
the disease processes. The connective-tissue fibers of the part, how- 
ever, are longest retained, and remain as a reticulum or tubercle stroma 
long after the other elements of the tissue have disappeared or been 
pushed aside. 




Fig. 38. — Foreign body tubercle in subcutaneous tissue, showing foreign body (wood) in 
the center and an atypical giant-cell. 

In soft tissues, such as the lungs, spread of tuberculous lesions is 
easy, and a diffuse inflammatory exudate may arise with only an occa- 
sional miliary tubercle. If several tubercles meet, their limiting walls 
may fuse and a conglomerate tubercle ensue. A conglomerate tubercle 
may also arise by the transportation of organisms from the center of 
an already formed focus, through its outer zone, by means of epithelioid 
cells or lymph-currents. 

Tubercles tend to coalesce, forming larger tubercular masses, and 
sometimes distinct tuberculous tumors are so produced. In the lower 
animals, particularly in cattle, such tuberculous tumors of the serous 
surfaces are not uncommon. They may simply stud the membranes, or 
they may hang as polypoid masses; the term "pearl disease" is applied 
to these cases (Fig. 39) . Somewhat similar tuberculous tumors are met 
with in human tuberculosis, especially in the brain (Fig. 40). As a rule, 
however, increasing areas of tuberculous disease of organs are only 



A TEXT-BOOK OF PATHOLOGY 




Fig. 40.— Bovine tubercle of pearl disease. 



INFLAMMATION AND REGENERATION 



145 



partly composed of tubercles, the bulk of the diseased area presenting 
evidences of ordinary or peculiar inflammatory changes to which the 
presence of the tubercles has stimulated the tissues. 

Again, in general lymphatic tuberculosis, one may see diffuse epi- 
thelioid and round-cell increase without special arrangement, but dis- 
placing or distorting lymph-gland architecture (Fig. 41). 




Fig. 41. — Tuberculous lymphatic gland: a, a, Lymphadenoid tissue; J>, b, large round 
cells (epithelioid) ; c, c, large spindle cells (Ziegler) . This is the diffuse form and bears 
resemblance to Hodgkin's disease. 

The tubercle bacilli in the earliest stages of the tubercle may be 
seen lying in the tissue and perhaps between the epithelioid cells first 
formed. With the evolution of the disease they are more and more 
abundant, are largely within the cells, and the giant-cells in particular 
may contain large numbers (Fig. 42). 
As the necrotic changes increase, the 
bacilli become less conspicuous, and 
eventually none may be visible. The 
existence of the bacilli, however, can- 
not be doubted, since injection of por- 
tions of such tubercles produces the 
disease in guinea-pigs. 

Syphilis. — -Histology. — In syphilitic 
processes of all kinds and in all of 
the stages there is a tendency to 
accumulation of round cells and pro- 
liferation of connective-tissue cells, 
the processes being first manifest 
around the smaller blood-vessels, but 
subsequently extending to other parts 
of the tissue. The walls of the blood-vessels themselves are frequently 
involved, and thickening of the inner or of all the coats may be ob- 
served. Complete destruction of the vascular channels is not rarely 
the consequence. Some authors locate the earliest changes in the small 
veins and lymphatics. In the subsequent course of the disease there is 
a tendency to the formation of distinct cicatricial connective tissue, 
10 




Fig. 42. — Giant-cell containing 
bacilli (from a photograph made by 
Dr. William M. Gray). 



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A TEXT-BOOK OF PATHOLOGY 



giving rise to indurated scars, strictures, or diffuse sclerosis; and a less 
pronounced tendency to the occurrence of degenerations, mucoid and 
fatty, causing areas of degenerative softening. 

The Chancre. — The initial lesion first presents small areas of round- 
cell infiltration in the deeper layers of the skin or mucous membrane 
and, as a rule, in the neighborhood of the blood-vessels. The connective 
tissue at the same time undergoes proliferative change, and. spindle- 
shaped cells or irregular embryonal connective-tissue cells are found 
mingled with the round lymphoid cells, or surrounding foci of the 
latter. Giant-cells are rarely present. Thickening of the blood-vessels 
may be observed in the later stages or from the very first. The tissue 
elements of the skin and of the subcutaneous tissue are usually sepa- 
rated by infiltrating liquid, and the latter may loosen the tissues of the 
surface and cause exfoliation of the superficial epidermis, and thus lead 
to the development of the primary vesicle or the erosion so commonly 




Fig. 43. — Gummatous meningoencephalitis (Ziegler). 



seen. The induration of the chancre is probably the result of the sclero- 
sis of the vessels and the general connective-tissue hyperplasia, as well 
as in part due to the tense infiltration of serous liquid. 

It is characteristic of syphilis that the periarterial change occurs 
first, to be followed by the parenchymatous. This process may go 
on during all the secondary stage. Obliterating endarteritis is a type 
of change in syphilis that may occur at any stage. 

The Mucous Patch. — The condyloma latum is very similar in struc- 
ture to the initial lesion. There is, first, round-cell infiltration of the 
deeper layers of the mucous membrane, with serous exudation and 
erosion of the surface. Later, there is a tendency to connective-tissue 
hyperplasia, though this is less marked than in the case of the chancre. 

The Tertiary Lesions. — The gumma is composed in large part of 
round cells derived from the blood-vessels and proliferated connective- 
tissue cells, having a spindle shape or various irregular forms. Epi- 



INFLAMMATION AND REGENERATION 



147 



thelioid cells are less abundant, and giant-cells, though occurring at 
times, are usually few in number. Plasma-cells may be abundant in 
syphilitic lesions, and mast-cells occur in small numbers. The blood- 
vessels are nearly always more or less affected, the intima being thick- 
ened and the adventitia being also involved to a variable extent. Peri- 
arterial 1 changes are very conspicuous. There is some new formation of 
blood-vessels, the lesion in this respect differing from the nodular lesion 
of tuberculosis (Fig. 43). Secondary changes are almost always seen 
in gummata of considerable dimensions, being more diffuse and irregular 
than in tuberculosis. Among these may be recognized a gradual 
necrotic transformation of the cells in the center of the lesion, with dis- 
tinct fatty degeneration or myxomatous change. The degenerated 
tissue may be infiltrated by leukocytes in a state of fair preservation. 
The differential diagnosis between a tubercle and a gumma is by no 
means easy, and there are cases in which it is well nigh impossible. 
Stains for the bacilli or the spirals should be used. 

In the diffuse tertiary lesions of syphilis the tissues of the affected 
organ are indurated, the connective tissue showing more or less pro- 
nounced hyperplasia. These processes cannot be certainly distinguished 
by their microscopical or general features 
from sclerosis due to other causes, unless 
there are associated miliary or massive gum- 
mata. 

Leprosy. — The nodule or leproma is a some- 
what indurated growth resembling the tubercle, 
but differing from it in its greater vascularity 
and in the absence of the tendency to cheesy 
necrosis. Microscopically, it is composed very 
largely of proliferated connective-tissue cells of 
different forms, plasma-cells, and endothelioid . Fig. 44.— Lepra bacilli 

ii -kt i i i i l- i • in a lepra cell (Rare and 

cells. J\ew blood-vessels are discovered in more Schmorl). 
or less abundance, the newly made tissue fol- 
lowing their course, and a tendency to complete organization with the 
formation of fibrous tissue may be seen in the character of the cells and 
the presence of fibrous intercellular material. Elastic fibers degenerate. 
The bacilli occur within the cells and possibly also between them, 
arranged either singly, in pairs, or in bundles like wrapped-up cigars. 
They are always found in groups and usually in large numbers. They 
multiply within the cells, the protoplasm of the latter at the same time 
undergoing a process of swelling and degeneration. This at first spares 
the nucleus, but finally the nucleus itself is broken down and the cell is 
thus converted into a sac containing degenerated protoplasm and 
abundant bacilli (Fig. 44). The term lepra cell has been given to these. 
The bacilli also occur in the connective-tissue cells, in fatty tissue, and 
very often in the adventitia of blood-vessels. Giant-cells may be 
formed, though they are not frequent and are rarely typical, being much 
vacuolated. In a pure lesion polymorphonuclear cells are usually 
absent. Secondary infections or injuries may lead to suppurative or 




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A TEXT-BOOK OF PATHOLOGY 



other forms of softening, and the final termination, either with or without 
previous softening, may be cicatrization. In some instances the lesions 
of the internal organs met with in supposedly leprous cases, notably 
those of the lungs, intestine, kidney, and serous surfaces, have been 
found avascular, with more tendency to necrosis and containing more 
giant-cells; in some of these cases inoculation has shown that the lesions 
contained tubercle bacilli. Whether these were strictly tubercles, or 
whether they were lepromata with secondary infection with tubercle 
bacilli, cannot be decided. They were certainly not pure leprosy, and 
more probably were purely tuberculous. 

The anesthetic areas and pigmented or light colored spots of the anes- 
thetic form present somewhat the same histological features as the leprous 
nodule, though in a diffuse form. Formerly these lesions were considered 
entirely the result of trophic changes. In these cases the more con- 
spicuous lesion is that of the nerves. These may show nodular thick- 
ening of the perineurium with inflammatory and degenerative changes 
of the nerve itself. The bacilli are present in these lesions, lying mostly 
within the cells of the perineurium. The effect is at first to irritate the 
nerve and later a compression and degeneration of the nerve-fibers. 
Changes in the spinal cord have occasionally been discovered. 

Glanders. — In acute glanders there is a local necrosis of the fixed 
tissues with a fibrillary or granular degeneration sprinkled with chroma- 
tin debris and surrounded by a zone of polynuclear leukocytes. The 
elastic fibers remain in good condition for some time, but finally swell 
and degenerate. In chronic glanders the nuclei are retained for some 
time and the cells present an epithelioid type. Considerable connective 
tissue is formed. Polynuclear cells, but not typical giant-cells, may be 
seen. 

Actinomycosis. — The first lesion of this infection is a simple sup- 
purative focus. This shortly assumes a tubercle arrangement by the 
appearance of giant- and epithelioid cells. It, however, soon proceeds to 
softening and central necrosis. The surrounding tissue is occupied by 
an active granulation process, losing all specific character except a tend- 
ency to fatty degeneration of the cells. The pus contains the sulphur 
granules of the organism, but the mycelium with its swollen end may be 
found penetrating the granulation tissue. . 

The histological changes in other streptothrix infections — mycetoma, 
pulmonary streptothricosis — are essentially the same. 

Rhinoscleroma. — The histological lesions of this condition are usually 
quite specific, although some authors still express doubt of the etiological 
importance of the Bad. rhinoscleromatis. The specificity of this chronic 
granulation tissue lies in the large Mikulicz's cells, a form of plasma- 
cell with hydropic or hyaline degeneration and a relatively small nucleus. 
They contain the bacilli. (See also page 303.) 

Saccharomycosis. — This condition gives rise to nodular necrotic 
masses surrounded by irregularly placed abundant giant-cells and active 
connective-tissue formation in the immediate neighborhood. The 
masses grow actively and may form considerable tumors. The budding 



INFLAMMATION AND REGENERATION 



149 



yeasts may be found in the pus and some are seen in the giant-eells. 
The more acute the process, the more necrotic. Chronic cases tend 
to show tumefactions. 

Sporothricosis. — The peculiarities of this granulation tissue consist 
in a diffuse growth of epithelioid and plasma-cells and connective tissue. 
There is no nodular growth. The new growth and its supporting struc- 
ture do not tend to undergo degeneration. 

Mycosis fungoides may be a granuloma. Its exact nature is as yet 
uncertain. Its discussion is found under the Tumors, p. 199. 

REGENERATION 

Definition. — The term "regeneration" is applied to the formation 
of new cells or tissues to take the place of those destroyed. Regeneration 
may be physiological or pathological. The former is that which occurs 
in the normal life of the organism and by which the cellular wear and 
tear is counterbalanced. Pathological regeneration is the more mas- 
sive and often atypical reconstruction follows disease or injuries. Re- 
generation is one of the essential elements in inflammation, as has been 
shown in the preceding pages, but it is not always an inflammatory 
process. 

Etiology. — The cause or mechanism by which normal regeneration 
is brought about is more or less obscure. The cells have an inherent 
tendency to multiply, and this goes on to a certain point, at which the 
normal development is complete. This limit is probably maintained by 
some restraining influence, but the nature of this is unknown. In the 
skin and mucous membranes, where physiological regeneration is most 
active, new cells are constantly produced and the older cast off. In 
what manner the balance is so maintained that production and de- 
struction keep their equal pace is as yet matter only for speculation. 
The idea of action and reaction occurs naturally to the mind, and it 
seems probable that the reproductive processes are dependent in some 
way upon the loss of substance. In some cases the normal restraining 
influence seems to be deficient and giant growth results. In all forms of 
normal or physiological regeneration the reconstructed cells are exactly 
like the pre-existing cells, and the status of the tissue is unaffected. In 
highly specialized cells, such as those of the nervous system, regenera- 
tion seems to be intracellular — that is, the cells are constantly rejuven- 
ated by supplies of nutriment rather than by reproduction in toto. It 
may be said in general that the lower the type of cell in specialization, 
the greater its power of self-propagation by cell division. The reverse 
is likewise true. A cell will also reproduce better when young and in 
its normal position than otherwise. 

In pathological regeneration there seems to be abnormal stimulation 
of the reproduction of cells as well as a reduced restraint. It is not 
improbable that various toxic substances have the power of stimulating 
the formative process, though this has not been actually demonstrated. 
In all cases in which degeneration is due to mechanical, thermal, or 



150 



A TEXT-BOOK OF PATHOLOGY 



toxic causes there is, first, destruction of cells, then regeneration. In 
such cases the relief from the accustomed pressure may serve as a with- 
drawal of restraint, but at the same time there is doubtless augmented 
formative energy. In other words, nature repairs defects in excess. 
The stimulus may be the same agency as that which caused the primary 
cell destruction, or it may be due to the influence of formative irritants 
derived from the dying and dead cells. The demonstration that micro- 
organisms are able to produce substances having a strong attractive 
or repellant influence upon leukocytes gives some warrant to the belief 
that similar substances are at work in the regenerative changes that 
accompany bacterial diseases. In the case of tissue destruction due to 
other causes similar products possibly play a part. It seems fair to 
assume from the work of Loeb and Miescher and others that certain 
conditions involving oversupply of protein and some alterations in 
chemical reaction in functionating tissues may be sufficient cause for 
proliferation. If this be true of relatively normal tissues, somewhat 
similar conditions may play a part in the proliferative changes occur- 
ring in pathological states. 

Pathological Anatomy. — In the normal regeneration of cells the 
process is one of gradual cell multiplication without marked changes of 
any sort. Pathological regeneration may be equally simple, but more 
often there are complicated changes in the pre-existing tissues and new 
formation of blood-vessels may precede or accompany the regeneration. 
The vascular regeneration is a necessary preliminary, having the pur- 
pose of supplying abundant nutriment to the tissues undergoing pro- 
liferation. 

Cell multiplication occurs in two ways, the direct and the indirect. 
The former method is one of simple cleavage, by which the cell is divided 
into two or more parts. This mode of division is unusual. 

Amitosis or direct cell division is a retrograde process in every in- 
stance. In some cases it is simply a fragmentation of the nucleus owing 
to altered conditions in the cell and probably not in any sense an at- 
tempt at cell division. When numerous fragments are formed, and 
some growth of the nucleus attends the process, giant-cells may result 
because the protoplasm does not divide. Evidences of degeneration of 
the protoplasm are apt to be met with in such cells. Of these, vacu- 
olization, granular or hyaline change, fatty degeneration, and even cal- 
cification may occur. 

The common method is called indirect segmentation, karyokinesis, 
or karyomitosis. In this method complicated changes begin in the 
nucleus and finally lead to division of the cell into two or, rarely, into 
several parts. It is unnecessary to refer to the histological stages in 
detail, but in a general way we may describe the process as follows: (1) 
The nucleus of the cell enlarges and the chromatin fibers become thicker 
and less closely woven than normally; (2) U-shaped loops of chromatin 
fibers arrange themselves around a central clear space or polar field to 
form a mother wreath; (3) these loops then undergo longitudinal cleav- 
age and the separated parts move one to one pole and the other to the 



INFLAMMATION AXD REGENERATION 



1.51 



opposite pole of the cell, forming daughter stars, which eventually become 
coarse and then fine skeins of new nuclei; (4) the protoplasm of the cell 
finally divides and the process becomes complete. 1 

Regeneration of Epithelium. — In its simplest form, as, for instance, 
after a very slight injury to the cornea, regeneration occurs by 
a direct replacement of the injured cells by multiplication of the cells 
of the same kind at the point of injury. The intact cells become some- 
what swollen, then undergo ordinary cell division, and new cells are 
formed. In the reconstruction of surface epithelium involving to some 
extent the underlying tissues, as in lesions of the mucous membranes 
or skin, the surface epithelium undergoes the same kind of multiplication 
as that just described, and the mass of new-formed cells dips down some- 
what into the space caused by the injury. In the deeper tissue new 
formation of connective tissue takes place in the manner already 
described under the head Healing of Wounds, and to be presently 
discussed more fully. In the subsequent stages the redundancy of 
epithelium caused by the dipping down of the mass of new cells into 
the injured area is reduced by condensation and gradual disappearance 
of some of the cells, so that eventually the epiderm or the layer of epi- 
thelium on the mucous surfaces does not differ from that in the surround- 
ing parts. When large areas of epithelium have been destroyed the 
replacement of the epithelial covering occurs by gradual increase of the 
cells at the periphery of the denuded area, until in time the whole surface 
becomes covered. When skin-grafting is practised by the surgeon, a 
similar growth of the epithelial cells starts from each of the grafts placed 
upon the denuded surface. The repair of defects in endothelial sur- 
faces follows the same general laws as lately shown by Carrel. In 
lymph-vessels the endothelium may regenerate or may possibly be in- 
volved in connective-tissue formation. 

Regeneration of Fibrous Connective Tissue. — In all cases of exten- 
sive injury the connective tissues take an active part in regeneration, 
and in the case of highly specialized tissues new-formed connective 
tissue takes the place of the specialized tissue, which itself is less capable 
of regeneration. There is almost always an excess of cellular reproduc- 
tion and consequently an enlargement of the part affected by the in- 
jury. Subsequently the cells contract, and thus the bulk of the new 
tissue approximates that destroyed. The new tissue must, of necessity, 
be more firm, as a larger number of cells are condensed in the space 
previously occupied by a less number. 

The important processes in regeneration of the connective tissues 
are: swelling and multiplication of the connective-tissue cells, migra- 
tion of the new cells into the area of injury, and the formation of new 

1 Abnormal Cell Division. — There are certain disorders of cell multiplication that 
may be here described. Karyokinesis, instead of being a regular process of division of 
the nucleus into two daughter nuclei, may proceed irregularly. Sometimes the process 
is asymmetric, i. e., does not lead to equal division; in other cases it is multipolar, several 
instead of two daughter nuclei resulting. Other less definite irregularities are some- 
times observed, and some have held that cell division may occur by a process of mixed 
karyokinesis and amitosis. It is important to recognize that some of the forms of nuclear 
degeneration (karyorrhexis. hyperchromatosis) may be mistaken for normal or abnormal 
karyokinesis. Pathological karyokinesis is most frequently seen in malignant tumors. 



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A TEXT-BOOK OF PATHOLOGY 



blood-vessels. The old connective-tissue cells increase in size and then 
undergo division by mitosis of the nuclei. As a result, new cells of 
rounded outline and with rather pale nuclei result. These may remain 
at the point of their formation or may actively migrate, like leukocytes, 
toward the center of injury. Subsequently they tend to undergo a 
change of form, becoming elongated and spindle-shaped or irregular in 
outline (Fig. 45). It is these cells, and not the polymorphonuclear 
leukocytes, which are active in the final restoration of the tissues, and the 
terms "formative cells" and "fibroblasts" are, therefore, appropriate. 
It is believed by most observers that endothelium can go over into con- 
nective tissue. It seems certain that this membrane has something to 
do with the organization of a thrombus. With continued irritation the 
cells change from a flat plate to almost a cubic form. When the new 
cells have been formed, increase of intercellular substance takes place. 
The fibrils may be derived from the 
cells themselves by separation of 
filamentous prolongations growing 
out from the pointed extremities of 
the spindle cells, or they may result 
from a cleavage of a homogeneous 
intercellular substance in which the 
cells are at first embedded. This 





Fig. 45, 



-Fibroblasts forming fibrous tissue 
(Ziegler) . 



Fig. 46. — Formation of new blood-vessels, 
as seen in the tail of a tadpole (Arnold). 



intercellular substance doubtless is a product or a secretion of the cell. 
In either case the fibrils are essentially a result of cellular activity. In 
the later stages of connective-tissue regeneration the fibrils contract, 
and the tissue thus becomes more compact, especially when the amount 
of intercellular substance is excessive. Collagen and fibroglia fibrils are 
reproduced and at some places also elastic fibers. The cells at the same 
time decrease in size and some are so compressed as to be almost ob- 
literated. It is characteristic of new-formed connective tissue, how- 
ever, that up to the latest stages the tissue is more cellular than normal 
tissue. 

According to Marchand three forms of round or lymphoid cells are 
also represented in connective-tissue regeneration : one the small lymph- 
cell, and two called leukocytoid cells. One of the two is somewhat 
larger than the small lymph-cell, possessing a relatively palely stain- 
ing nucleus, and considerable slightly granular or vacuolated protoplasm. 
This is the polyblast of Maximow and it may come from the blood- 



INFLAMMATION AND REGENERATION 



153 



stream or the tissue cells. The third variety is the plasma-cell, which 
has been described on p. 122. 

Giant-cells of the foreign body or proliferative type are common in 
regeneration, and they act as phagocytes to remove substances which 
are not dissolved. 

New formation of blood-vessels is an important factor in regenera- 
tion of connective tissue when the extent of injury has been consider- 
able. Repair of very trifling injuries, such as an incised wound followed 
by a close apposition of the injured surfaces, does not involve any new 
formation of blood-vessels, though the pre-existing vessels become some- 
what hyperemic. When the injury is more extensive, vascularization is 
a necessary step in the repair. The new vessels result from extensions 
from the pre-existing vessels (Fig. 46). The endothelium of the cap- 
illaries becomes swollen and here and there processes are sent outward. 
These may unite with similar processes from adjacent capillaries 
or from the same one at a point somewhat distant, and central vac- 
uolization may convert the loop into a primitive channel which event- 
ually becomes a fully formed capillary by multiplication of the endo- 
thelial nuclei and formation of definite endothelial cells. Sometimes the 
new vessel is formed by parallel outgrowths from adjacent endothelial 
cells of the parent capillary, leaving a space between the new-formed 
cellular extensions. Such new vessels occur around the site of injury and 
project in the form of loops into the area of injury itself, being sur- 
rounded by the new-formed connective-tissue cells above described. 
Usually the area of injury is first filled with a blood-clot or coagulated 
exudate derived from the injured tissues. This forms a matrix in which 
the new-formed connective-tissue cells migrate and the capillary loops 
project. The clot or coagulated exudate is subsequently absorbed as 
the process of cellular replacement advances. The young connective 
tissue thus formed later contracts and the small blood-vessels are largely 
reduced by compression, so that the appearance of the tissue may become 
that of a quite avascular structure. 

In regeneration of connective tissues, elastic fibers are not observed 
in the earlier stages. Subsequently they are formed more or less abun- 
dantly. 

Regeneration of cartilage and bone takes its origin from the peri- 
chondrium in the former case and from the periosteum or marrow in the 
latter. The process begins as a proliferation of chondroblasts or osteo- 
blasts respectively, which have the power to lay down a matrix which 
attracts chondromucin or bone-salts, as the case may be. The adult 
bone and cartilage cells have not the power to regenerate. In both 
instances embryonal connective tissue, such as that which occurs in 
regeneration of fibrous connective tissues, is first formed. Later, in the 
case of cartilage, areas of homogeneous intercellular substance appear, 
and thus cartilaginous substance is developed. Very commonly, how- 
ever, regeneration of fractures of cartilages is mainly fibrous, and there 
may be little if any true cartilage. Regeneration of bone in the case of 
fractures proceeds in much the same fashion, an abundance of cellular 



154 



A TEXT-BOOK OF PATHOLOGY 



tissue first appearing around the fractured ends of the bone, within the 
marrow cavity at the point of fracture, and between the broken ends of 
the bone. In this embryonal connective tissue branching and radiat- 
ing columns of rudimentary osseous tissue appear as a sort of network 
in which complete ossification occurs at subsequent stages. Later, 
much or all of the embryonal tissue around the fracture and within the 
marrow cavity is absorbed, and the repair of the fracture is made com- 
plete by thorough ossification of the part between the ends of the bone. 
When bone-salt deposit is deficient, cartilaginous union results. 

Regeneration of adipose tissue begins with a formation of fat-free 
cellular tissue. Later the cells become infiltrated with fat. 

Regeneration of Muscle Tissue. — Striated muscle after injury or 
excision is capable of some regeneration by, as a rule, amitotic multi- 
plication of the muscle nuclei. The area of destruction if considerable 
is first occupied by regenerating connective tissue into which irregular 
protoplasmic projections from the ends of the divided muscle-fibers 
extend. Subsequently these elongate and form new muscle-fibers, but 
they are apt to be narrow and more or less irregularly arranged, so that 
the regeneration is rarely complete. 

Regeneration of smooth muscle by mitosis takes place in some cases 
(uterus) , but connective-tissue formation occurs instead when the areas 
of destruction are large. 

Regeneration of Glandular Organs. — In epithelial glandular organs, 
such as the liver, kidney, mammary or salivary glands, considerable 
new formation of epithelial cells may take place. It has been taught 
that gland cells are replaced by tissue cells below the basement-mem- 
brane. This is undoubtedly incorrect. Glandular cells are recruited from 
glandular cells or occasionally from the cells of small ducts. In the 
liver there may be active proliferation of cells and formation of new 
biliary ducts. This is seen in experimental injuries and also in asso- 
ciation with some forms of cirrhosis. In the case of the kidney, re- 
generation may occur in the cells of the straight tubules, while in the 
mammary glands, salivary glands, and the smaller glands of mucous 
membranes new formation of acini and ducts proceeds from the smaller 
excretory ducts of the affected glands. In this way an atypical glandular 
structure may result. This will be discussed under Adenoma. Skin 
glands and their outlets are regenerated if the fundal parts have not 
been destroyed by the surface damage. 

Regeneration of Nervous Tissue. — Nerve-fibers are capable of con- 
siderable regeneration, which proceeds from the sheath of Schwann. 
The medullary substance is differentiated within the sheath, and the 
new axis-cylinder is an outgrowth from the existing axis-cylinder or 
the nerve-cell. Regeneration of the nervous fibers in the brain and 
cord takes place to but a slight extent. Injuries here are usually 
repaired by the formation of new connective tissue and regenerating 
glia. The large multipolar nerve-cells seem to be capable of intra- 
cellular repair after partial injuries, but complete regeneration is never 
accomplished. It is possible, however, that they may be capable of 



INFLAMMATION AND REGENERATION 



155 



limited proliferation, as such cells occur in certain tumors. Neuroglia 
proliferates, but less readily than fibrous tissue. 

Pathological Physiology. — Regeneration is the more or less effective 
effort of nature to replace injured or excised tissue. The restoration is 
complete in proportion as the tissues lack in higher organization and 
differentiation. The younger the individual, the more complete the 
regeneration of his tissues; and the lower the type of tissue, the more 
complete will be its restoration. In glandular organs, though some pro- 
liferation of epithelial structures occurs, the new-formed glandular ele- 
ments are but little capable of glandular activity. Newly developed 
nervous tissue is least capable of restoring the original function. 

METAPLASIA 

This is the term applied to the transformation of one form of tis- 
sue into another without the intervention of a stage of regeneration 
by cellular multiplication. It is exemplified under normal conditions 
by the transformation of cartilage into bone. It occurs with great fre- 
quency under pathological conditions, and may be here described as a col- 
lateral or inferior specialization in a tissue of the same original character, 
for mutations of tissue types do not occur. Thus, cartilaginous tissue may 
have an abnormal deposit of bony salts, fibrous tissue may become bony 
or fatty or myxomatous, but these never become glandular structures, 
nor does gland tissue ever become nervous tissue. The process may be a 
purely interstitial affair and the cells suffer secondary changes. In other 
cases of metaplasia the cells may be primarily altered, as when ordinary 
connective tissue is changed to fatty tissue. 

The process, except where accommodative or defensive, is not easily 
understood. Cells of the embryo destined to be epithelium are differ- 
entiated so that they may assume their adult normal form and func- 
tion; by metaplasia one type of epithelium may adopt the form and at 
times the function of another. The same facts are true for connect- 
ive-tissue cells. Fully differentiated fibrous tissue may become calca- 
reous without the agency of osteoblasts from bones, connective-tissue 
cells acting the role of the latter. 

Although it has been claimed that fat cells are descended from the 
mucoid embryonal cells, some observers seem to think that connective- 
tissue cells not descendants of these fetal elements may become fat 
cells by metaplasia. 

The metaplasia of epithelial cells, as, for example, a change from cylin- 
drical to squamous cells on the surface of mucous membranes, has been 
doubted by some authorities. They assume that such apparent trans- 
formations are due either to ingrowths of the new order of cells from sur- 
rounding areas or by enlargements of islets of mucosa covered with 
such cells. Experiments, as those of Fiitterer, however, indicate that 
metaplasia does occur. In this process not only the old epithelia are 
altered by the changed conditions, but the new-formed epithelia, under 
the altered conditions of environment, develop into the new order of 
cells rather than into the parent form. 



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A TEXT-BOOK OF PATHOLOGY 



The causes of metaplasia are, naturally, changes in physical relations, 
including alterations of pressure and irritation, carrying with them some 
differentiation of function and changes in nutrition. Injury or chronic 
irritation may bring these factors into play. Examples of metaplasia 
are to be found in the change of the bladder epithelium to a horny 
layer from a calculus; the flattening of the bronchial epithelium in 
bronchiectasis; the appearance of calcareous deposits in chronically in- 
flamed connective tissues, especially around joints. Changes similar 
to these repeatedly occur in neoplasms. 

The term retrograde change (Ribbert) has been applied to an altera- 
tion of cells in which under pathological conditions a lower order of differ- 
entiation is assumed, but in which the new order of cells do not acquire 
specific characteristics of a different sort. Thus, cylindrical epithelia of 
glandular tubules may be changed to cuboid cells lacking the original 
functional characters and not possessed of a new function such as would 
be the case with squamous cells. Similarly, in the atrophy of striped 
muscle, non-striated, narrow fibers with abundance of nuclei give evi- 
dence of a retrograde change toward embryonal conditions. 



CHAPTER VI 



PROGRESSIVE TISSUE CHANGES 

This term may be used to designate pathological conditions in which 
there is a tendency to the formation of new and functionally active 
tissue. 

HYPERTROPHY 

Definition. — The term "hypertrophy" is applied to a pathological 
condition in which a certain part increases beyond the normal size, 
without marked alterations from the normal structure. The term 
hypertrophy is frequently used loosely to designate enlargements of 
various kinds in which but one tissue of an organ is increased, or in 
which there is deposit of abnormal exudate. Such instances are not, 
strictly speaking, cases of hypertrophy. 

Etiology. — The causes of hypertrophy are quite numerous. In 
some cases there is a distinct increase of functional demand brought 
about in some way or other, as in the hypertrophy of the muscles of 
athletes; in the hypertrophy of a kidney after disease or removal of 
its fellow; or in the hypertrophy of a limb after injury to the opposite 
limb. The direct increased demand for work occasions the hypertrophy. 
Sometimes there appears to be a special tendency to hypertrophy, as is 
evidenced by the occurrence of congenital or hereditary giant growth. 
Most of these, however, are instances of peculiar and abnormal develop- 
ment, rather than of hypertrophy, the latter being a condition developed 
pathologically in parts previously well formed. Disturbances of the 
nervous system and internal secretions may play a part in the develop- 
ment of some hypertrophies, but these influences are obscure. Con- 
tinued congestion undoubtedly stimulates tissue growth, but this ele- 
ment is the means whereby hypertrophy is effected rather than the 
original cause. 

In the compensatory or vicarious functional hypertrophies we must 
assume that two factors are at work — first, the stimuli resulting from 
increased demand, and second, the adaptive mechanism of the part ad- 
justing reaction to stimulation. It may be further assumed that there 
is always a margin of safety between the work thrown upon a part and 
the limit of work possible. During continued activity the cell enlarges, 
for which it must have increased nutrition and some period of rest. 
Should the stimulation continue without rest and increased nutrition, 
degeneration may occur. 

Some of the hypertrophies, such as that of the breast during preg- 
nancy and lactation, are undoubtedly due to internal secretions, prob- 
ably of ferment nature. The hormones belong to this class. We may also 

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include in a similar group the growth taken on by some organs, like hair- 
follieles and mammae, at puberty. Derangements of the ductless glands 
may lead to hypertrophies, among which the most conspicuous example 
is acromegaly from disease of the hypophysis. 

Pathological Anatomy. — Parts the seat of genuine hypertrophy 
are uniformly increased in size. This is well seen in the condition 
termed "giant growth," or "gigantism," in which the bony framework 
and other tissues may be uniformly affected, the individual growing 
to excessive size. Sometimes local giant growth of the skeleton and 
external tissues is observed, as in the case of one member or a single 
finger. This has often been found in corresponding members on the two 
sides of the body. In certain cases termed "hypertrophy," in which this 
designation is more or less justified, lack of uniformity in the increase of 
the organ or part affected causes irregular increase in size. Hyper- 
trophy and hyperplasia may be used by the economy to make up loss 
of bulk the result of disease. 

Histologically, hypertrophy may be simple or true hypertrophy, 
and numerical (hyperplasia). In the former there is increase in the size 
of the individual cells; in the latter the cells increase in number, though 
the individuals are not excessive in size, and, indeed, often smaller than 
the normal cells. In the hypertrophy of the uterus during pregnancy 
and of the heart muscle in compensatory enlargement, simple hyper- 
trophy predominates. Hyperplasia is very commonly a factor in hy- 
pertrophy of any kind, but may be so strictly limited to one tissue of an 
organ, notably the connective tissue, that the term "hypertrophy" 
is in no way applicable. Between these extremes there are all grades 
of cases, in many of which it is difficult to determine whether the desig- 
nation hypertrophy is applicable or not. In some cases the clinical 
designation hypertrophic enlargement is used, though the condition is 
strictly one of hyperplasia of the connective tissue, with a tendency 
rather to atrophy than hypertrophy of the proper substance of the 
organ. Instances of this are hypertrophic cirrhosis of the liver, some 
cases of hypertrophy of the heart muscle, etc. 

Pathological Physiology. — Hypertrophy results from an increased 
demand upon an organ or member, and leads to increased functional 
capacity. Thus, in the case of a diseased kidney, the opposite kidney may 
be capable of compensating for the deficiency; in the case of laborers 
the enlarged muscles may meet every demand made upon them. There 
are occasional instances of more or less genuine hypertrophy resulting 
from diseased conditions, in which the excessive functional capacity 
causes marked disturbances, as, for example, in case of enlargement of 
the thyroid gland. 

TUMORS 

Synonyms. — New Growth, Neoplasm, Pseudoplasm. 

Definition. — In its broadest etymological significance the term "tu- 
mor" designates an abnormal swelling in any part of the body. This 
definition, however, is not applicable to tumors in the ordinary sense. 



PROGRESSIVE TISSUE CHANGES 



159 



Inflammatory growths and collections, such as abscesses, hyperplastic 
deposits, and the like, are excluded. Pathologists, however, have al- 
ways found it difficult to construct an accurate definition for tumors or 
to draw sharp lines of separation between them and the inflammatory 
or infectious swellings that occur in various diseased conditions. An 
attempt to establish an ultimate boundary-line is evidenced by the 
term autonomous new growtlis, applied by Thoma. This name is used to 
designate the supposed spontaneous origin of new growths and their 
independence of ordinary causes, such as are recognized in the production 
of inflammatory outgrowths and the like. It cannot be said, however, 
that tumors are causeless, and in the discussion of the etiology we shall 
have occasion to refer to certain definite factors known to aid in their 
production. It is true, however, that the growth of tumors is practi- 
cally always out of proportion to the amount of local irritation or to the 
severity of other factors that may be conceived as playing some part in 
the etiology; and in the great majority of cases the causes, whatever 
they may be, are obscure or unknown. A negative definition perhaps 
best suits for the delimitation of this term "tumor." Thus, we may ex- 
clude from the category of tumors all swellings in which some sufficient 
cause is discoverable, and include the apparently causeless growths 
among the true tumors. A further characteristic of tumors is their 
independence. Excepting the blood-supply, there seems to be no de- 
pendence on the organism in which they occur, and they contribute noth- 
ing to the continuance of its life and its integrity. Nor is there any 
apparent restraint to the indefinite growth of the tumor comparable to 
that which keeps normal growth and even pathological processes of other 
kinds within certain bounds. 

Despite all of these characteristics, there are cases in which pathol- 
ogists cannot determine positively whether certain growths are to be 
classified as tumors or some other conditions. 

Etiology. — A great number of theories have been suggested to 
explain the causation of tumors. 

Among the older w T riters there was a disposition to attribute the 
occurrence of tumors to a constitutional dyscrasia, or a diseased state 
of the fluids of the body, a cause as obscure as the tumor. 

Recently a number of more elaborate theories have been con- 
structed that resemble this older one, in ascribing the growths to some 
form of disturbance of vital activity and of cell proliferation, without 
explaining the cause of such disturbance. For example, we may refer 
to the theory that tumors result from a retrograde change in vital proper- 
ties of certain cells, so that they tend toward the original characteristics 
of the germ-cells and multiply in a purposeless and indeterminate man- 
ner. This theory was based upon the fact that asymmetrical karyo- 
mitosis is frequently observed in tumors. It was assumed that in this 
unequal division of the cells the peculiar, differentiating qualities of the 
cell are cast off with the smaller portion, causing the larger, in the course 
of several generations, to become anaplastic or retrograded. It has, 
however, been shown that the same sort of asymmetrical mitosis also 



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A TEXT-BOOK OF PATHOLOGY 



occurs in non-tumorous conditions; and an additional factor that must 
enter into the theory, the nature of the stimulus that causes the ana- 
plastic cells to proliferate actively, is wholly unexplained. 

According to the late observations by Slye upon mouse tumors, neo- 
plasms represent "a manner of growth" transmissible to progeny in a 
Mendelian sense, the faulty character being dominant or recessive, so 
that by proper mating it can be made to remain a dominant inherited 
feature or to die out. 

Another theory would explain the occurrence of new growths some- 
what upon the basis of infection, assuming, instead of an exogenous 
infection with micro-organisms, an endogenous infection. This was sug- 
gested by the discovery of leukocytes within the tumor-cells. The 
author of this theory explains that in consequence of some thermic, 
chemical, or other irritation certain cells may become, so to speak, infec- 
tious, assuming the role of a sperm-cell and stimulating the adjacent 
cells to abnormal multiplication. Such theories, however, are entirely 
speculative, and leave the etiology as little settled as before. 

Virchow strongly advocated the theory of external irritation, and was 
able to cite numerous examples of tumors that had arisen in consequence 
of more or less definite traumatism. Thus, in cases of carcinoma of the 
breast, in the epithelioma occurring on the lips in pipe-smokers, and in 
the epithelioma of chimney-sweeps, there is at times a definite history 
of unusual irritation, and the relation of cause and effect seems easily 
traceable. It must be admitted, however, that there is some further 
underlying cause which renders one individual liable to tumor growth, 
while another is not thus predisposed, and though it is probable that 
some tumors owe their origin to irritation as the exciting cause, all 
cases cannot be thus explained. 

Cohnheim advanced the interesting theory that defective develop- 
ment lies at the basis of tumor formation. According to his theory, there 
are frequently small errors of development leading to the inclusion or 
misplacement of portions of the original blastoderm in the midst of tis- 
sues derived from a different layer of the embryo. These inclusions, or 
embryonic rests, are independent of the function of the part in which they 
lie, and are assumed to be liable to subsequent sprouting, with the con- 
sequent formation of tumors. There is evidence that this theory con- 
tains a certain measure of truth, and some tumors, as, for example, 
certain ovarian growths, tumors of the parotid region, and others, seem 
to originate in this way. The theory, however, is not by any means 
universally applicable, and it leaves unexplained the final proliferation 
of the embryonal rests that had previously remained dormant. The 
assumption, however, that such rests would quite readily take on active 
growth as a result of various simple irritations, or when the vitality of 
the part was stimulated, is less forced than that which would attribute 
such proliferative activity to cells in their normal relation to surrounding 
tissues. Similar conditions may be brought about by disease or injury 
of various tissues. This is the essence of Ribbert's "disturbance of tissue 
tension" theory. If certain cells or parts of the tissue are displaced 



PROGRESSIVE TISSUE CHANGES 



161 



from their normal relations to the surrounding structures, the same 
conditions are established as by the embryonal displacement of por- 
tions of tissue. Not improbably this sometimes occurs either as a 
result of accident or of disease, and subsequently the displaced por- 
tions may prove the starting-point of tumor growth. Some authorities 
have insisted upon this as a frequent occurrence and as explanatory of 
many tumors. Experiments have shown that certain types of epi- 
thelium (epidermis), both adult and fetal, as well as certain fetal con- 
nective tissues (cartilage), may be experimentally removed from their 
normal position and implanted in another part of the same animal and 
still retain their potentiality of growth. Such transplanted fetal tissues 
do not continue to reproduce the fetal stage, but tend to reproduce the 
ultimate stage of the transplanted tissue. Furthermore, in no case has 
there been found any infiltration of surrounding tissues by trans- 
planted tissue, nor any tendency to metastasis. All of this shows that 
there is something additional in the development of tumors beyond the 
mere dissociation of structures from the surrounding tissues. 

Hansemann's theory, based upon the defective mitotic figures seen 
in tumors, assumes that this want of normality causes the cell function 
to be disturbed and it fails to undergo its proper specialization (ana- 
plasia), so that it becomes parasitic; it is itself the parasite. Oertel also 
assumes the primary change to be in the nucleus, there being a removal 
of part of the chromatin. Adami's modification of Hauser's theory 
assumes that the cell which started the growth lost its specialization, 
but not its power of reproduction. The relief of other demands upon 
it permitted the cell to apply all its energy to the dominant remaining 
function and acquire the habit of growth. This theory is at least con- 
sistent with our knowledge that a tumor serves no useful purpose to the 
body. Yet it must not be forgotten that as far as we know tumor-cells 
are nourished and have a cell chemistry closely like normal cells. They 
are at least dependent upon the same pabulum, although the end-prod- 
ucts may be different. 

Recently an infectious character has been ascribed to malignant and 
benign growths, and there is no doubt that in certain respects tumors 
resemble infectious processes of definitely ascertained kinds. Their 
effect upon the general health and their tendency to metastasis are 
very significant facts. Furthermore, the discovery that various patho- 
logical processes characterized by nodule formations resembling tumors 
in gross appearance are, in reality, infectious growths lends color to the 
suspicion. The resemblance of such growths to tumors is, however, 
merely superficial. As far as metastasis is concerned, tumors differ 
notably from infections, for, in the former, parts of the growth itself 
are conveyed to some place at a distance from the starting-point, there 
to proliferate and occasion a metastatic nodule; while in the case of 
infections the micro-organisms alone are carried to the secondary situa- 
tion, where they occasion changes in the local cells similar to those found 
in the original focus. 

Numerous investigations have been made to determine a possible 
11 



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A TEXT-BOOK OF PATHOLOGY 



connection of bacteria with tumors. These have proved beyond doubt 
that no bacterium of ordinary sort has any such relation. The possi- 
bility of ultramicroscopical organisms and even of such as, through ex- 
cessive parasitic character, could not live except within cell hosts, has 
been considered. 

Secondary and accidental invasions of bacteria into tumors may 
occur, and sometimes confusion has been occasioned by this circum- 
stance. 

Various investigators since Hanau have found it possible to trans- 
plant certain tumors from man to animals or from one animal to an- 
other. This has sometimes been interpreted as an evidence of the 
infectiousness of tumors, though with doubtful propriety, since the trans- 
plantation of the tissue from one site to another, like the phenomenon 
of metastasis, proves only the proliferative tendency of the cells of the 
growth and not, of necessity, any infectious origin. The transplantation 
of part of the tumor from one animal to another or from one part to 
another in the same animal does not differ from the transference of por- 
tions of the tumor to distant places in ordinary metastasis. 




a b c d 

Fig. 47. — Inclusions in cancer cells: a and b, early stages of "parasitic" bodies; c, late 
stages, showing division by segmentation; d, cancer cell containing leukocytes (Ruffer). 

The experiments of Rous have shown that certain tumors of the 
fowl may be transmitted to a susceptible bird by suspensions of cells or 
a filtrate from this suspension which has been passed through a porce- 
lain filter that would hold back bacteria. He assumes that for these 
tumors there is a contagium vivum. These viruses only produce the 
kind of tumor from which they come. 

In carcinomata and other epithelial new growths, as well as in 
sarcomata, certain forms of supposed animal parasites have been de- 
scribed. In 1889 Thoma found in the protoplasm and nuclei of car- 
cinoma cells bodies which he regarded as coccidia; and about the same 
time Malassez and Albarran found similar structures in the cells of an 
epithelioma of the maxilla. Darrier found bodies of the same kind in 
Paget's disease of the nipple, and many subsequent investigators have 
described similar formations. Among these supposed protozoan or- 
ganisms some are intranuclear, some extranuclear, and some wholly ex- 
tracellular. 

All sorts of bodies have been described in tumors, and to them their 
respective observers have clung tenaciously as the cause of neoplasms. 
They have no relation to the causation of tumors, for they have not 
withstood close investigation. Figures 47 and 48 show some of those de- 



PROGRESSIVE TISSUE CHANGES 



163 



scribed. Members of many protozoal and arthropodal genera have been 
described, even to as large a parasite as Sarcoptes. Many of the 
smaller ones were doubtless artefacts or can be ascribed to the Chlamy- 
dozoa of Prowaczek. The larger ones were artefacts or accidental in- 
clusions. We may still learn that such protozoan or metazoan organ- 
isms have something to do with neoplasms, judging from Fibiger's results, 
but we are not yet prepared to accept any of them as the cause. 

Recently blastomycetes have been thought of some etiological im- 
portance in the causation of carcinoma, but a careful review of the 
literature is convincing that the evidence does not 
suffice to establish any such connection. Blastomy- 
cetes do not constantly occur in malignant tumors, 
and when present are not in such numbers or in such 
relation to the tissue as to establish an etiological 
significance. The lesions definitely known to be due 
to blastomycetes are of entirely different character 
from those of tumor growths, being strictly exuda- 
tive and inflammatory, with proliferation of endothe- 
lium and connective tissue, such as occurs in infec- 
tious inflammations. The proliferation of epiderm 
seen in the blastomycetic skin lesions of man is en- 
tirely secondary to the chronic inflammation of the 
underlying tissues. The latest important communi- 
cation upon the relation of organized bodies and Fig. 48.— Rhopa- 
new growth comes from J. Fibiger, who found nem- !£atosus US C (Korot- 
atodes in a papillomatous glandular gastric cancer neff). 
of wild rats. These nematodes are carried by the 
roach, Periplaneta americana, and can be transferred to unaffected 
rats, when, if the animal be susceptible (not all are), a carcinoma of 
constant type will be produced. 

Predisposing Conditions. — Whatever may eventually prove to be 
the immediate cause of tumors, it is certain that predisposing causes are 
often of great importance. The occurrence of certain forms of tumors 
in persons of advanced age and in persons whose vitality has been re- 
duced by disease gives evidence that a constitutional predisposition 
is sometimes requisite for the formation of the new growth. The nature 
of this vital defect has sometimes been speculated upon, and retrograde 
vital metamorphosis of the cells or other like changes have been assumed 
to occur. These theories, however, are purely speculative. In some 
cases there is evidence of a family predisposition, and heredity was 
formerly regarded as of great importance. While this element cannot 
be entirely denied, it has certainly been overestimated. 

The Structure of Tumors. — In their histological structure tumors 
do not differ absolutely from healthy tissues. In all cases they conform 
more or less with the structure of some one or more tissues. The cells 
composing tumors invariably represent some one or several types of 
normal cells, though they may differ in being larger or smaller than the 
normal cells, or in being of embryonal or' undeveloped character. 




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A TEXT-BOOK OF PATHOLOGY 



It may be said that the tissue from which a tumor arises is revert- 
ing to a state from which perfect differentiation into the normal adult 
structures cannot or does not occur. They have not lost all differ- 
entiation or specialization, since glandular tissue will always produce 
tumors with a glandular basis, but what is lost keeps the tissues near 
the parent or embryonal cell type. 

Not infrequently asymmetrical and otherwise abnormal mitosis of the 
cells is observed. Some reference to the varieties of such mitoses will be 
found in the section on Cellular Necrosis (p. 104). It is important to note 
that such mitoses are not confined to tumors, but occasionally occur in 
inflammatory and infectious cellular proliferations. 

In the arrangement of their cells tumors differ greatly from normal 
tissues, and they may be described as being atypical proliferations as far 
as their organic or tissue arrangement is concerned. The orderly dis- 
position of cells and stroma or intercellular substance seen in the normal 
tissues and organs is wanting, particularly in the tumors in which 
organic arrangement is simulated. There may be in some cases entirely 
typical glandular acini, but the relation of these to each other and the 
absence of regularly disposed excretory ducts render the tissue, as a 
whole, atypical. 

In the histological examination of tumors it is customary to find 
scattered through the stroma and between the tumor cells various forms 
of leukocytes, especially the polymorphonuclear forms and lympho- 
cytes. The imperfect development of the walls of blood-vessels of 
tumors permits of ready emigration of leukocytes, and there is, there- 
fore, in practically every tumor a certain amount of leukocytic infil- 
tration. Sometimes leukocytes are found in enormous numbers; and 
when a tumor undergoes inflammatory change, massive accumulations 
and abscess formations may be met with. Plasma-cells, which are prob- 
ably altered lymphocytes, are sometimes conspicuous, and mast-cells 
(basophilic granular cells of doubtful significance) are sometimes 
found in benign as well as in malignant tumors. They are frequently 
abundant near the edges of the growth. Eosinophilic leukocytes are 
occasionally quite numerous. The leukocytes are often found within 
the tumor cells in the form of inclusions. These, doubtless, have been 
mistaken for parasites in some instances. 

The blood-vessels of tumors have comparatively fragile and poorly 
developed walls. In the malignant growths or rapidly developing tumors 
of any sort the vessels are mere spaces between the tumor cells, with 
little attempt at the development of firm walls. Tumors do not appear 
to have special nerves. Lymph-vessels are variable. In some they are 
well developed, having been included and modified from pre-existing 
ones; in others they are entirely lacking. 

Regenerative changes are constantly met with in tumors. In this 
way the connective-tissue framework of the growth is formed just as 
such tissue is normally produced, and in this process elastic as well as 
ordinary connective tissue may be formed. In rapidly growing malig- 
nant tumor the framework of the tumor is, for the greatest part, derived 



PROGRESSIVE TISSUE CHANGES 



165 



from the pre-existing connective tissue of the affected part, and only 
in very small measure from regeneration of connective tissue. 

The structure of tumors is always closely related to that of the 
tissue from which it springs, a primary tumor invariably growing in 
a part in which there is tissue of the type simulated by the tumor, and 
it is from this tissue, doubtless, that the tumor takes its origin. A con- 
nective-tissue growth invariably springs from a part in which connective 
tissue of some form has pre-existed, and epithelial growths, from 
a part in which there has been epithelium. Transformation of one 
variety of tissue into another variety, with the production of a hetero- 
logous tumor, does not occur. This statement, though applicable also 
to secondary tumors, is sometimes difficult of demonstration from the 
fact that the secondary growths take origin from cells transported to 
the seat of the metastatic growth, though not normally found in the 
part in which the secondary tumors have arisen. The occasional dis- 
covery of a primary tumor in a locality in which the form of tissue 
composing the tumor does not occur may be explained upon the assump- 
tion (based on some actual demonstrations) that embryonic rests had 
been deposited at the seat of the tumor by faulty development. 

The Shape of Tumors. — This depends to a large extent upon 
their manner of growth, their situation, and the influence of surround- 
ing parts. We may distinguish, first of all, between circumscribed and 
infiltrating growths. The former may be of various shapes, but are dis- 
tinguished by their sharp delimitation and often by the existence of a 
distinct capsule; the latter are indeterminate, and the extent to which 
they involve the healthy tissues cannot be accurately determined. Cir- 
cumscribed tumors usually grow centrally or in an expansive manner, 
the new cells being produced in the interior and gradually pushing the 
older parts outward toward the surrounding tissues. The infiltrating 
growths are eccentric in development, and may result from a gradual 
extension of parts of the periphery of the original growth, or by the 
development of secondary nodules in the neighborhood which become 
confluent with the original mass. Of the circumscribed growths, we 
may distinguish small nodules of spherical or ovoid form buried in the 
substance of the tissue or projecting from some surface as more or less 
hemispherical elevations. These may be large or small, and the terms 
miliary, tubercular, nodular, and the like are employed to designate the 
individual grades. When a tumor projects from the surface in such 
a manner that the projecting part is larger than the part between the 
projection and the surface of the body or the organ involved, the term 
fungiform or fungoid tumor may be applied, while in the cases in which 
the new growth is attached by a more or less narrow pedicle the name 
polyp or polypoid tumor is applicable. Wart-like growths are known 
as verrucose or papillary tumors, and those in which a distinct cauli- 
flower form is developed are called dendritic. 

The Number of Tumors. — Primary tumors are usually solitary 
at their onset, though examples of multiple primary growths, such as 
carcinoma involving both breasts simultaneously, or simultaneous 



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A TEXT-BOOK OF PATHOLOGY 



appearance of carcinomata or sarcomata in different parts of the mucous 
membrane or elsewhere, may be observed. In these cases it is often 
likely that there was a single tumor at the very onset, with secondary 
growths originating before the primary growth had reached any con- 
siderable magnitude. Primary benign tumors are usually solitary, but 
sometimes may be found in considerable number, and there may be 
enormous numbers scattered in various parts of the body. Thus, in 
cases of multiple enchondromata or multiple fibromata the number may, 
from the first, be very great. 

Secondary tumors are usually multiple. In most cases the number 
of nodules found postmortem or during life is considerable, and some- 
times they are so numerous that large portions of the body may be 
literally studded with new growths. This is seen very well in the 
secondary sarcomatous or carcinomatous nodules involving the peri- 
toneum and the other serous surfaces, in which cases the degree of 
involvement is equalled only by that seen in miliary tuberculosis. 

The rate of growth of tumors is extremely variable. Those in or 
consisting of dense tissue tend to grow slowly, while those of more 
cellular nature in looser parts grow more rapidly. There may be periods 
of entire cessation of growth. No rule can be laid down for any group 
of new growths. 

Instances of multiple primary tumors of different kinds are on 
iecord. For example, carcinoma and sarcoma may occur in the same 
individual as can epithelioma and adenoma. 

Pathological Physiology. — In most cases tumors take no part in 
the functional life of the part in which they occur or of the individual. 
What influence they may bear to the general metabolism is as yet prac- 
tically unknown. Cases, however, are recorded in which large lipo- 
matous or other tumors have been found to suffer practically no change, 
while the individual in whom they occurred was undergoing progressive 
emaciation from starvation. That there is a certain amount of function, 
however, in some cases is shown by the fact that biliary pigment is 
detected in the cells in certain carcinomatous tumors of the liver, or 
abortive milk formation in cancers of the breast. It may be that the 
want of proper organic arrangement, and particularly the. lack of 
excretory ducts, accounts for the lack of function; but, whatever the 
cause, it is certain that, as a rule, the functional activity is practically 
nil, or at all events perverted. The occurrence of large quantities of 
glycogen in certain tumors is perhaps of interest as indicating an attempt 
at functional activity, but is more probably significant only of active 
proliferation. With very few exceptions it may be said that tumors are 
entirely parasitic, living at the expense of the organism and contributing 
nothing to its development or nutrition. 

Certain tumors disturb the general health. This result may be 
due to secondary degenerative or inflammatory changes dependent 
upon lack of nutrition or upon irritation and bacterial infection. The 
progressive cachexia of carcinoma is still unexplained, though in some 
cases hemorrhage and interference with organic function play a part. 



PROGRESSIVE TISSUE CHANGES 



1G7 



The chemical constitution of tumors and the relation this bears to 
the body in general and to the changes in body fluids are subjects that 
have had very important advances in the past few years. They have 
led to better understanding of the place of a tumor in the body, if not 
to its etiology. As has been said, the chemistry of tumors is closely like 
that of the tissue from which they spring. This is also true of metas- 
tases. There has been no isolation from tumors of substances that are 
peculiar to them in general or to any particular variety. Because of 
their high cell content some tumors contain much nucleoprotein, but 
this will vary as the parent tissue varies. The digestion products of 
these proteins are abundant because autolysis is active within tumors. 
Glycogen also accumulates in tumors because of lowered cellular ac- 
tivity. It is, of course, in highest amount in tumors, the original tissues 
of which naturally store it. Enzymes of the parent cells are retained in 
neoplasms. 

The inorganic elements are present in the proportion of the proteins 
that they help to form, and not specifically otherwise. 

Enzymes are said to be more abundant in tumors than in normal 
tissues, and the extensive autolysis of new growths certainly bears this 
out. Some observers assert that the ferments are different or peculiar 
to tumors, but this is not proved. Tryptic action is very prominent; 
so much so, indeed, that carcinoma patients develop a high antitryptic 
power in the blood. Many tumors have the power of continuing the 
natural internal secretions of the parent tissue. Thus, thyroid and 
adrenal tumors and their metastases may produce colloid and epinephrin 
respectively. 

It may be that the cachexia of cancer patients is due to a constant 
dissemination of the products of autolysis. 

Some of the products of tumor growth and extracts of the new tissue 
have hemolytic properties, but the exact relation of this power to anemia 
and cachexia is not understood. Metabolism is essentially the same as 
in wasting disease in general, there being an excessive excretion of pro- 
tein degradation products and mineral salts except the chlorids. 

Tumors fail to set up any constant immune bodies that protect the 
system against them. The normal blood has a low anticancer-cell 
power and blood-serum of cancer patients has a lower value. Immunity 
tests, such as complement fixation and precipitation, are sometimes 
present, but too variable to permit any conclusions as to their value for 
diagnosis or relation to etiology. 

Tumors may be classified as benign or malignant. The former do 
not affect the general health of the patient in any notable degree, and 
are dangerous mainly by reason of the pressure they may exert on 
vital structures or the secondary changes (hemorrhages, softening, 
suppuration) to which they are liable. Malignant tumors generally 
disturb the general health from the first, and, in addition, tend to recur 
after removal and spread to other parts of the body (by direct invasion 
or by metastasis through the circulation or lymphatic channels) . 

Metastasis, or the transplantation of a tumor from one part of the 



168 



A TEXT-BOOK OF PATHOLOGY 



body to another, may occur in several ways. The growth may invade 
surrounding lymphatic or venous channels, and extend in a linear 
manner sometimes to considerable distances. Thus, a growth of the 
neck may extend in the jugular vein and vena cava as far as the right 
heart. More commonly, single tumor cells or small numbers are 
carried as emboli along the lymphatic or venous channels to some new 
location, where a secondary growth results. Some tumor cells, especially 
of the connective-tissue type, are said to be capable of independent 
ameboid movement; this would favor penetration into capillaries. A 
third method is that in which parts of the tumor are spread over free 
surfaces, such as the peritoneum or pleura, and thus occasion new foci. 
Sometimes, though rarely, this happens on mucous surfaces also. 

Occasionally tumors that are ordinarily benign recur after removal 
or cause metastasis. The former circumstance is not infrequent in 
the case of nasal polypi and keloids of the skin ; the latter in the case of 
adenomata of the thyroid gland, chondromata, leiomyomata, hemangio- 
mata, and occasionally some others. The manner of growth (central 
proliferation) doubtless accounts for the infrequency of metastasis of 
benign tumors. 

Tumors have been known to disappear spontaneously. This is 
rare in human beings, but is commoner in animals suffering from either 
spontaneous or experimental tumors. The cause is not known. Tumor 
cdls are susceptible to mechanical influences when directly applied. 
They are more susceptible to .r-rays and direct sunlight than normal 
cells. These agents destroy the vital ferments, but not the autolytic 
ones. Pressure upon and injury to a tumor seems to favor metastasis. 

It has been suggested that injury favors metastasis because endo- 
thelial proliferation succeeding a trauma supplies a stroma in which a 
tumor cell may conveniently lodge and multiply. 

The terms primary and secondary tumors refer to the original and 
the metastatic growths respectively. 

Classification of Tumors. — No very satisfactory classification 
is possible at the present time, and it is unlikely that any will be 
constructed until more definite knowledge regarding the etiology is 
obtained. The older classifications were based upon the shape, the 
physical properties, or the nature (whether destructive or harmless) 
of various forms. Virchow offered a classification based on the histol- 
ogy of the new growths (histogenetic classification). According to this 
classification, fibroma, osteoma, chondroma, lymphoma, and sarcoma 
are included under the heading of connective-tissue tumors or tumors 
reproducing more or less accurately connective tissues. The different 
forms of tumors comprising the group are distinguished by their resem- 
blance to one or another of the forms of connective tissue. Among the 
epithelial growths are papilloma, adenoma, and carcinoma, and in the 
same group should be placed glioma, which, though it superficially re- 
sembles connective-tissue tumors and arises from the neuroglia, a tissue 
resembling connective tissue in function, is really an epithelial growth, 
as the neuroglia is an ectodermal derivative. Among the tumors re- 



PROGRESSIVE TISSUE CHANGES 



169 



producing muscle tissue are the two forms of myomata — the leiomyoma 
and rhabdomyoma. 

This classification is eminently satisfactory in some cases, but fails 
in the case of mixed tumors containing a variety of tissues and in which 
the primary or essential constituent is not always obvious. Thus, in 
papillomata it is sometimes difficult to determine whether the growth 
was originally epithelial or originally of connective-tissue type. 

Recently it has been suggested (Mallory) that a more careful study 
of the histological differentiation of the cells and intercellular substance 
may serve as a basis of classification of tumors. Three forms of fibrils, 
called neuroglia, myoglia, and fibroglia fibrils, have been distinguished, 
and have respectively been found in gliomata of various types, in leio- 
myomata, and in connective-tissue growths, including fibromata, fibro- 
sarcomata, and spindle-celled sarcomata. The fibrils differ sufficiently 
to form the basis for the recognition of the character of the cells from 
which they originate, irrespective of the rate of growth or physical 
properties of the tumor. 

Other pathologists have grouped tumors according to the embryo- 
logical derivation of the tissues from which the new growths originate or 
of the tissue composing the tumor. It is perhaps wisest to attempt no 
classification of any kind, and in the following sections we have ar- 
ranged the various tumors according to their histological characters, fol- 
lowing in a general way the adult tissue types without attempting to 
establish groups. 

Connective-tissue Tumors 
fibroma 

Definition. — A fibroma is a tumor composed of connective-tissue 
cells and fibers resembling those seen in fibrillar tissue. 

It is derived from mesodermal cells which have the power to produce 
various kinds of fibrils. It varies from a slowly growing tumor composed 
of fibers almost exclusively up to rapidly growing new growths composed 
of cells, with little tendency to proceed to fiber formation. In the lat- 
ter case it approaches a sarcomatous nature. 

Etiology. — The causes of fibroma are as obscure as those of 
tumors in general. There are many facts, however, which point to 
the importance of irritation or injury as exciting causes. Among these 
may be mentioned the development of peculiar forms (keloids) in scar 
tissue and the resemblance of these tumors to spontaneous fibromata, 
and the appearance of fibrous nodules in the skin at points of friction 
or definite pressure or in places irritated by discharges. 

It is impossible to draw sharp lines between fibromata and hyper- 
plasias of connective tissue following irritation. In the skin and super- 
ficial tissues there occur hyperplastic connective-tissue processes, con- 
stituting elephantiasis, which in some cases are distinctly the result 
of irritation, and in other cases seem purely spontaneous. The ele- 
phantiasis of tropical countries, often due to occlusion of the lymphatic 



170 



A TEXT-BOOK OF PATHOLOGY 



channels by filarise, and the thickening of the skin and adjacent con- 
nective tissue of the legs around old ulcerations or eczematous areas, are 
instances in which distinct irritation is the cause. On the other hand, 
congenital elephantoid conditions of the skin are seemingly spontaneous 
or causeless, and some of the cases in later life have the same char- 
acteristic. The diffuse hyperplasias of the viscera, though often dis- 
tinctly inflammatory, may appear without adequate discoverable cause, 
and, according to the view of some authorities, are to be looked upon 
as diffuse fibrosis or fibromatosis, rather than as inflammatory condi- 
tions. In ordinary cases of sclerosis of the organs the connective-tissue 
growth is entirely diffuse, but thickenings may occur in certain situa- 
tions, and the resemblance to tumor formation is then much more 
striking. This is sometimes the case in the liver, but particularly in 
the kidneys. In the breast there are cases in which no dividing line 
can be drawn between chronic interstitial mastitis and fibroma. The 
microscopical appearances are practically identical. A distinction, if 




Fig. 49. — Hard fibroma (Warren). Fig. 50. — Soft fibroma of the subcutaneous 

tissue. 



any can be made, is based upon the nodular character and spontaneous 
origin in the one and the opposite conditions in the other. 

Appearance. — The naked-eye appearance of fibromata is usually 
quite characteristic. The tumor may be hard (Fig. 49) or soft (Fig. 
50), according as it resembles dense or loose connective tissue in struc- 
ture and according to the amount of edematous liquid or associated 
myxomatous degeneration of the intercellular substance. The growth 
is more or less rounded and usually enclosed in a distinct capsule. In 
the substance of organs it is spherical or tuberous, and when near the 
surface projects more or less. When it springs from a mucous or serous 
membrane or from the skin the weight of the tumor may gradually lead 
to a polypoid formation. Some of the fibromata of the skin are arbores- 
cent or dendritic in form, and keloids are frequently irregular or star- 
like in outline. The rounded and encapsulated tumors may be lobu- 
lated, though more frequently they occur in a uniform mass. 

Seats. — The points of origin from which fibroid tumors arise are 



PROGRESSIVE TISSUE CHANGES 



171 



very numerous, though they always spring from pre-existing connect- 
ive tissue. Among some of the more common localities may be men- 
tioned the subcutaneous connective tissue, the submucous tissue, the 
periosteum of bones, tendons and tendon-sheaths, and the fibrous 
covering of nerves. Of the internal organs, the uterus, the ovaries, the 
kidneys, and heart muscle are the most important. Less frequently 
fibromata are found in the serous membranes of the chest and abdo- 
men or of the central nervous system. The fibroids of the skin, uterus, 
the nerves^ (see Neuroma), and the mucous membrane of the nose are 
the most important. 

The mammary gland presents several interesting forms of inflam- 
matory or fibromatous new growth. First, there is a diffuse form of 
interstitial mastitis in which the entire breast becomes indurated; this 
is distinctly inflammatory. In other cases nodular or lobular areas of 
thickening occur, and in these the evidences of inflammatory action 
are sometimes obscure or wholly wanting. Some of these are certainly 




Fig. 51. — Intracanalicular fibroma (Perls). 



instances of true fibroma (fibroma mamma 3 nodulum). In still another 
group of cases the fibromatous proliferation of the connective tissue 
projects into the tubules and acini of the gland, pushing the epithelium 
before it and sometimes sprouting or proliferating in polypoid form 
within the tubules. The gland in such cases may present a striking 
macroscopical appearance on section. Numerous cystic formations may 
be visible, with projecting dendritic formations within, causing an appear- 
ance somewhat like that of a section through a cauliflower (Fig. 51). 
Microscopically, the proliferations of the connective tissue between 
the tubules and projecting within the tubules constitute the charac- 
teristic features. The term intracanalicular fibroma has been given 
to such cases. Obstruction of the tubules in certain areas may lead 
to very marked cystic distention. Combinations with sarcoma are 
frequent. 

Structure. — The definition explains the structure of fibromata. 
On section through the body of the tumor the fibrous nature may be 
revealed by a distinct concentric or radiating striation, particularly 



172 



A TEXT-BOOK OF PATHOLOGY 



in the case of hard fibromata. The softer varieties are much less likely 
to present this feature. The color is usually gray or whitish, and may 
be glistening when there is mucous degeneration, or yellow in the case 
of associated fatty tissue. Microscopically, a striking feature is the 
connective-tissue cell, which is rounded, star-like, and branching in the 
softer tumors, and compressed, spindle shaped, or elongated in the case 
of the hard varieties. Some authorities maintain that they are merely 
different stages of the same process. There are all gradations in this 
series. The intercellular substance is composed of a fibrillar network 
and homogeneous or granular material traversed by thin-walled blood- 
vessels, ofttimes having merely an endothelial coat. The parallel and 
wavy bundles of fibrils are the most conspicuous feature of hard fibro- 
mata. In softer varieties the fibrils are less often in bundles, and are 
twisted or irregularly curled. The fibrillar substance may be so closely 
packed that the intercellular substance has a glistening, hyaline appear- 
ance. This is very marked in keloids. Sometimes actual hyaline change 
affects the fibrils. Cavernous dilatation and rupture of the vessels may 
cause a distinct hemorrhagic appearance of the section, but such con- 
ditions are rare. 

A true keloid is a fully formed connective tissue tumefaction without 
a capsule and tending to show hyalin degeneration. It is commonest 
in negroes. The epidermal layers and papillae are correctly preserved. 
A false keloid arises in scar tissue. It is apt to show a limitation, but 
not by a distinct capsule, and the epidermis and papillae are absent or 
distorted. 

Secondary Changes in Fibroma. — In some cases embryonal 
round cells may be abundant and a distinct sarcomatous transforma- 
tion of the tumor may occur. This, however, is rare. In other in- 
stances, as has already been remarked, myxomatous tissue may be 
conspicuous, and all grades of transformation, from a pure fibroma 
to a pure myxoma, may be met with, especially in the case of soft 
fibroma. Fatty degeneration of the cells and lipomatous infiltration 
or associated lipoma are also frequent. These forms, the myxomatous 
and lipomatous, are particularly frequent in the submucous and sub- 
cutaneous connective tissues. Calcareous change occurs in large fibro- 
matous tumors, particularly in those of the uterus, and very rarely true 
ossification has been reported. Less commonly association of fibroma 
with other forms of tumor growth is found. Among these the com- 
bination of fibroma with leiomyoma is usual in the uterus. 

Small fibromata about nerve-endings may be hard or soft. Some 
arise from the connective tissue of the nerve-sheath or from Schwann's 
membrane. A kind occurring on the skin in disseminated form is 
called molluscum fibrosum. There is also a painful variety upon or 
near nerve-endings. The nerve-fibers pass through or are caught by 
the fibroma and are not themselves changed. 

Nature. — Fibroma is essentially a benign tumor, though recurrence 
occasionally takes place after removal, this being particularly the case 
with keloids and some of the polypoid growths of mucous membranes. 



PROGRESSIVE TISSUE CHANGES 



173 



In some of these instances there is undoubtedly a resemblance to sar- 
coma, if not actual sarcomatous transformation. As a rule, fibroid 
tumors are destructive only in so far as they are capable of producing 
mechanical injury by pressure. The growth of the tumors is usually 
exceedingly slow. Metastases of pure fibroma do not occur, and the 
mass does not recur if removed completely. 



MYXOMA 

Definition. — Myxoma is a tumor composed of connective-tissue 
cells and an intercellular substance containing mucoid material in more 
or less abundance. The gelatinous substance of Wharton in the um- 
bilical cord and the vitreous humor of the eye are normal tissue types 
which myxomata resemble in their structure. 

Etiology. — The causes and the nature of myxomata are prac- 
tically the same as those of fibromata, and intermediate forms make it 
difficult to draw a sharp line between the two. Less frequently myxo- 
mata are sarcomatous growths with myxomatous change. 

Appearance. — A typical myxoma is a soft, more or less flabby 
growth, enclosed by a capsule and having a rounded outline. It may 
project from the surface of the body or of an organ as a hemispherical 
elevation, or may hang by a narrowed pedicle in the form of a distinct 
polyp. The latter is frequent in the mucous membranes, but may occur 
in the skin as well. Sometimes the tumor is lobulated, and the lobules 
may be visible or may be easily felt. 
Occasionally myxomatous growths r 
are diffuse, having no capsule and 

marked by no definite limits. *> IP^ 

Seats. — Among the common 
situations are the subcutaneous and V - 

submucous tissues and the connect- 
ive tissues of certain organs, notably % a 
the mammary glands. They may 
occur along the course of nerves, 
and in the brain or the spinal cord. 
They sometimes spring from sub- 
serous tissues, notably from the in- 
terauricular septum and valves of 
the heart. The tumor mav be soli- 

, i-i £u i , Fig. 52. — Myxoma, showing stellate 

tary or, like fibroma, may be met ce n s separated by a gelatinous (mucoid) 

with in numbers. Congenital myx- intercellular material. 

oma has frequently been found. 

Structure. — Microscopically, the characteristic features are stellate 
or spindle-shaped connective-tissue cells which lie within a matrix of 
myxomatous material (Fig. 52). The latter is homogeneous or slightly 
granular, and somewhat refractive to light, giving the surface a glisten- 
ing quality. The cells themselves may be entirely normal young con- 
nective-tissue cells, or they may present evidences of fatty degenera- 




n 



174 



A TEXT-BOOK OF PATHOLOGY 



tion. Round, connective-tissue cells are met with in some instances, 
either scattered through the tumor or in certain areas, and may be so 
abundant as to justify the term "myxosarcoma." The vascular supply 
is usually poor, and the blood-vessels resemble those of fibroma in being 
only partially developed. Association with fibroma and lipoma is fre- 
quent. Cartilaginous tissue may be found in myxomatous tumors of the 
parotid gland or testicle, and in these cases the myxomatous portion is 
rather an association than a degeneration of an original chondroma. 
Myxomatous degeneration of chondromata, osteomata, fibromata, and 
sarcomata is, however, a frequent occurrence. 

Nature. — Myxoma is benign like fibroma, but recurrence is not in- 
frequently observed, and in a few instances metastasis has been reported. 
In these cases the growth was doubtless sarcomatous, with associated 
mucoid tissue. When myxoma becomes sarcomatous the cellular 
content increases and the mucoid material is absorbed. The growth of 
myxomata is slow. 

LIPOMA 

Definition. — A lipoma is a tumor composed of fatty tissue like that 
of the normal subcutaneous tissue. The epiploic appendages of the 
intestines are the normal type which lipomata resemble. They are 
derived from the fat cells and not from fibroblasts. The fat is the same 
as 1 natural subcutaneous adipose tissue in chemistry, except that the 
lecithin is somewhat less in amount. 

Etiology. — There seems to be a tendency, consisting perhaps in some 
derangement of the trophic nervous system, to the growth of these 
tumors. It is difficult at times to draw a sharp line between circum- 
scribed lipomata and diffuse fatty growth. Localized fatty or myxo- 
lipomatous accumulations in myxedema and a curious and apparently 
causeless deposit of fatty tissue sometimes observed in the subcutaneous 
tissue of the neck in men, represent the border-line between lipomata 
and ordinary obesity. Some individuals have a marked liability to 
constant overgrowth of fat in different parts of the body, and the term 
"lipomatosis" is not inapplicable. This fatty growth does not appar- 
ently depend upon the character or quantity of food, nor even upon 
sedentary life in some cases, but rather on an obscure tendency to 
adipose accumulation. The importance of the hypophysis and gonads 
to such conditions has been the subject of much fruitful investigation 
in recent years. 

Traumatism seems to play no part in the etiology of lipoma, though 
fatty infiltrations are prone to occur around areas of injury or disease 
and in degenerated organs. 

Appearance. — Lipomata are usually circumscribed and encap- 
sulated tumors having a lobulated character, the latter being due to 
septa of connective tissue. On the surface of the body they appear as 
somewhat hemispherical elevations which may reach enormous propor- 
tions. Rarely they become polypoid. In the interior of the body, as, 
for example, when they arise in the submucous or subserous connective 



PROGRESSIVE TISSUE CHANGES 



175 



tissue, they are very frequently, though not always, polypoid. Some- 
times they become detached and may be retained in one of the cavities 
of the body as free bodies. On section, the appearance is that of fatty 
tissue, though in some cases it is more firm from the association of fibrous 
tissue, and in other cases less firm from the nature of the fatty tissue 
itself or from associated myxomatous change. Lipomata may be soli- 
tary tumors or there may be many. As a rule, they appear in adult 
years or middle life, but congenital lipomata are not very rare; occa- 
sionally they are found to begin in childhood. 

Seats. — Among the situations in which lipomata occur the most 
common are the subcutaneous fatty tissue of the back, shoulders, 
buttocks or limbs, the submucous and the subserous tissues. They 
may arise either in the normal fatty tissue or in connective tissues in 
which fat is not normally present. Some authors, however, deny the 
possibility of lipomata arising excepting from pre-existing fatty tissue. 
Of the organs, the mammary gland and the kidney are most frequently 
involved. 

Structure. — Microscopically, lipomatous tumors resemble the normal 
fat. It is notable that the cells are larger — that is, contain more oil — 
than the normal fat cells, and this is strikingly the case in some instances, 
but is not always demonstrable. The vascular supply is about the same 
as in normal fat, though occasionally large vessels with thin walls are 
seen. Associated myxomatous or fibrous change may cause a variation 
of the microscopical appearance. Lipomata may undergo softening from 
necrosis, but more frequently become calcareous in part or completely. 

Nature. — This is the most benign form of tumors. Recurrence 
after more or less complete removal does, however, at times occur. 
A lipoma is dangerous only from its weight or position. It does not 
contribute to the support of the system in case of starvation. 

XANTHOMA 

Definition. — This term is applied to two possibly distinct though 
similar forms of new growth. The xanthoma vulgare occurs most fre- 
quently in the eyelids and may be confined to that situation. The 
growth appears in the form of flat elevations of a yellow color. Gener- 
alized xanthoma beginning about the eyes is less frequent. Xanthoma 
diabeticorum is a similar affection of diabetic patients. It occurs at a 
more advanced age, is more distinctly inflammatory, the masses are 
more rounded, and the eyelids and face are rarely affected. Xanthoma is 
frequently associated with hepatic disease. 

Structure. — The histology of xanthoma is that of modified fatty 
tissue. It resembles embryonal adipose tissue, and there is usually 
more or less round-cell infiltration as well. Some authors regard the 
latter as a tendency to sarcomatous change; others look upon it as 
inflammatory. It lies chiefly in the corium, but the subcutaneous 
tissue may be involved. Cholesterol combinations have been found in 
these tumors. 



176 



A TEXT-BOOK OF PATHOLOGY 



Nature. — Xanthoma is eminently benign. The diabetic form is 
subject to sudden and apparently causeless involution. The ordinary 
form may similarly subside, though much less commonly. 

CHONDROMA 

Definition. — A chondroma is a tumor composed largely or entirely 
of cartilage. The parent cell is, of course, the chondroblast in the 
perichondrium, a fibroblastic cell which has, in addition, the power to 
lay down a ground substance of chondromucin. When this predominates 
in tumors they have a hyaline appearance, but when the fibers pre- 
dominate the resulting mass follows the white fibrous or yellow elastic 
cartilage types. It is difficult to draw a sharp line between outgrowths 
of cartilage from existing cartilage or bone due to irritation from definite 
and independent tumor-like growths. A group of cases of intermediary 
character is that including cartilaginous nodules formed in tendons of 
muscles subjected to frequent irritations, as in the deltoid muscles in 
soldiers carrying heavy arms, and in the adductor muscles in the thigh 
in horseback riders. In these cases normal connective tissue seems to be 
directly transformed into cartilage, though the influence of irritation 
is undoubted. 

Etiology. — A congenital disposition, sometimes hereditary, is un- 
questionably present in certain cases. Virchow maintained that chon- 
dromata often spring from remnants or islands of cartilage left in ab- 
normal situations, as in the midst of bone, as the result of imperfect fetal 
development. The same explanation would account for parotid chondro- 
mata on the assumption that parts of the branchial arches are misplaced 
and remain in the substance of the parotid gland. Other evidences of 
the truth of the theory are the frequent occurrence of chondromata at 
the epiphyseal ends of bones, and the appearance of such growths in 
early life and especially in rachitic individuals. 

Irritation has been referred to. Direct traumatism is sometimes 
the cause of cartilaginous outgrowths from bone, particularly when 
fractures have occurred. 

Appearance. — Two distinct forms may be considered, and these 
are somewhat different in appearance. They are: (1) cartilaginous 
outgrowths, ecchondroses or ecehondromata, and (2) cartilaginous 
tumors or chondromata proper, originating in non-cartilaginous tissues. 

Ecehondromata present themselves as encapsulated, rounded, or 
somewhat irregular outgrowths from cartilages. Sometimes they are 
wart-like in form, and may occur in rows or groups. They may be firmly 
attached, or may be loosely united to the cartilage from which they 
spring. The most frequent (though not strictly neoplastic) are the 
outgrowths in the articular cartilage occurring in chronic arthritis, par- 
ticularly in arthritis deformans. Occasionally they become detached 
after their formation, and in the joints may thus become free bodies. 
More characteristically tumor-like ecehondromata originate from the 
surfaces of the laryngeal cartilages or from the costal cartilages. 



PROGRESSIVE TISSUE CHANGES 



177 



Chondromata proper most frequently occur in bones or the peri- 
osteum, and have a rounded or lobular appearance. 

Chondromata springing from the inner surface of bones (possibly 
originating from the marrow itself) may grow uniformly by repeated 
or constant proliferation and occasion globular swellings of the affected 
bones (Fig. 53). The true bony covering becomes more and more thin 
until it may actually be perforated. 

The true chondromata are usually rounded bodies of dense elastic 
consistency and the pale blue color of cartilage; they present lobular 
irregularity when they reach considerable size, the lobules being sepa- 
rated by connective tissue. 

Chondromata are usually hard, though secondary softening may 
occur. Incases in which association of mucous, sarcomatous, or other 
soft tissue is present the consistency is correspondingly less. In some 
cases central softening leads to 
cystic formation. The liquid in 
the cyst is more or less turbid and 
occasionally sanguinolent. 

Seats. — Ecchondroses and 
chondromata, for the most part, 
take their origin from bone, carti- 
lage, or periosteum. The ecchon- 
dromata originate from the peri- 
chondrium rather than from the 
cartilage itself. In some cases 
chondromata originate in connect- 
ive tissue, as that of the tendons, 
by a process of cartilaginous meta- Fig 53 ._chondroma of the thumb (War- 
plasia. Cartilage tumors are met ren). 
with in some of the glandular 

organs, notably the parotid gland, testicle, and ovary; and rarely they 
occur in the lungs, especially at the root and springing from the peri- 
bronchial cartilages. 

Ecchondroses are most frequent about the long bones, as those 
of the extremities, and particularly at the epiphyseal attachments, 
where they may reach considerable proportions. Situations of great 
clinical importance are the interpubic and occipitosphenoidal junc- 
tions. In the former situation ecchondroses projecting inward may 
interfere seriously with labor, and in the latter place cartilaginous out- 
growths may penetrate the dura and exercise injurious compression on 
the brain. Allusion has been made to the ecchondroses of the joints 
in arthritis. 

Chondromata proper may occur in the neighborhood of bones, in 
the muscles and tendons near their bony attachments, and in the 
organs mentioned, but in the last situation are rarely pure, myxoma 
being the most frequent associate. 

Structure. — Chondromata resemble hyaline, fibrous, or elastic car- 
tilage, the first named being much the most frequent. The tissue 
12 




178 



A TEXT-BOOK OF PATHOLOGY 



differs from normal cartilage in the fact that the cells are frequently 
without capsules and are much less regularly arranged (Fig. 54). The 
intercellular substance is more abundant, and is frequently gelatinous, 
mucoid, or fibrous, and not rarely the different types of cartilage occur 
within narrow limits. Association with myxoma and sarcoma, or both, 
is common, especially in the parotid and testicles, the proportion of the 
several ingredients varying greatly. Tumors of this kind are spoken of 
as mixed tumors. Calcification and true ossification are not infrequent, 
particularly in cartilage tumors intimately connected with bone. The 
term osteochondroma is applied in such cases. The name osteoid chon- 
droma is applied to chondromata in which the intercellular substance 
is trabecular in arrangement, suggesting bone structure, but in which 
actual ossification has not occurred. Such growths are met with about 
the bones and, as a rule, spring from the periosteum. The cartilag- 
inous part of these tumors is without blood-vessels. 




Fig. 54. — Chondroma of the hyaline type. 

Degenerative changes are frequent because while the tumor as a 
whole is vascular the islands of cartilage are not, and the parts removed 
from the vessels get little nutrition. Myxomatous degeneration may 
occur, though myxoma is more frequent as an association than as a 
degeneration. Softening may occur in the center of the mass, and may 
lead to cyst formation, this being particularly common in the myxo- 
chondromata. Growths of this kind are frequently quite vascular and 
hemorrhages into the cysts may occur. Eventually such cases may show 
scarcely any cartilage cells, a few being perhaps detected in some part of 
the cyst wall. A single hard lump may be left at one side of the cyst, the 
rest of the tumor having softened. 

The more cellular the tumor, the greater the tendency to sarcomatous 
degeneration. Fibrillation and cell increase are early indications of such 
a change. 

Nature. — Chondromata are usually benign, and are dangerous only 
through the pressure they exert. Removal of a part of the tumor may 



PROGRESSIVE TISSUE CHANGES 



179 



have a beneficial influence in causing calcification of the remainder. 
Metastasis may undoubtedly occur in pure chondromata through 
transportation of particles in the circulation; such cartilaginous emboli 
have often been demonstrated. The secondary growths are most fre- 
quent in the lungs. Metastatic chondromata are, however, more fre- 
quently chondrosarcomata than pure chondromata. 

OSTEOMA 

Definition. — An osteoma is a tumor composed of osseous tissue. 
Osteomata are closely allied to cartilaginous tumors, and frequently 
transformations occur. The cell of origin is the osteoblast, as adult 
bone cells do not reproduce. 

Etiology. — The same difficulty is experienced in distinguishing in- 
flammatory outgrowths or exostoses from true bony tumors, as in the 
case of cartilaginous growths. Enlargement of the facial bones in 
leontiasis ossea, of the bones of the extremities in acromegaly and 




Fig. 55. — Exostoses of the elbow-joint. 



hypertrophic pulmonary osteo-arthropathy, and ossification of the 
muscles in myositis ossificans, are instances of border-line conditions 
separating true tumors from inflammatory hyperostoses. Irritation 
and traumatism undoubtedly play a part in the etiology, even in neo- 
plasms unattached to the bone, and in the case of bony outgrowths 
injury is generally the immediate cause. An underlying predisposition 
undoubtedly exists, and explains the occurrence of congenital multiple 
bony tumors. 

Appearance. — Two forms may be distinguished, as in the case of 
chondromata: (1) outgrowths or exostoses and osteophytes, and (2) 
the osteomata proper, or heteroplastic osteomata. Exostoses and osteo- 
phytes are distinguished one from the other by their shape and appear- 
ance rather than by any essential difference. The former are direct 
outgrowths of more or less wart-like character; the latter are more ex- 
tensive and present the appearance of bony deposits upon bones, and 
are less closely attached (Fig. 55). In both forms the surface of the 
growth is irregular, nodulated, or wart-like (Fig. 56). The consistency 



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A TEXT-BOOK OF PATHOLOGY 



is that of bone, and the size varies from that of small outgrowths to 
masses as large as a fist. On section, two forms may be distinguished: 
the hard or osteoma durum, after the nature of compact bone with fairly 
well imitated architecture; and the soft or osteoma spongiosum, after 
the character of spongy bone, but less well arranged, more of the em- 
bryonic cell type and more apt to show degenerative changes. Some- 
times the substance of the tumor is exceedingly dense, and the term 

osteoma eburneum is applied. This form 
is without the completed Haversian sys- 
tems, and osteoblasts are apt to be 
wanting over large areas. 

There may be osteomata of endosteal 
origin arising from endosteum or mis- 
placed cartilage. 

The heteroplastic osteomata, or those 
separated from the bone, are more 
rounded and, when of considerable size, 
usually nodulated and lobulated. In 
the serous membranes they occur as flat 
bony plates. 

Fig. se.-osteoma of the lower jaw Seats.— Osteomata spring from the 
(Warren). bone or cartilage, or from connective 

tissue near the bones. More rarely they 
arise in other connective tissues, in the serous membranes, or in certain 
organs, notably the testicle and parotid gland. 

Osteomata connected with bones are most frequent about the 
epiphyses, at the attachments of muscles, or at the seat of old frac- 
tures from which abundant callus has been deposited. The skull 
bones may be affected on the outer or inner surface, and often an ele- 
vation is noted without and within at the same spot. A form of clinical 
importance is that in which exostoses occur on the inner aspect of the 
metatarsal bone of the great toe from compression of tight shoes. In 
the maxillary bones osteomata may originate about the roots of mal- 
formed teeth. In cases of accumulation of cement substance beginning 
at the neck of the tooth the term dental osteoma is applied; these are 
strictly comparable to osteomata. In cases in which proliferation of the 
dental pulp has occurred the term odontoma is applicable, and the 
tumor is not of osseous character. The bony growths sometimes seen 
in the serous surfaces nearly always arise in areas in which there has 
been thickening from chronic inflammation. They are most frequent 
in the dura mater of the brain, particularly the falx cerebri, though the 
membranes of the cord, the pleura, endocardium, or pericardium may 
be involved. 

Structure. — Microscopically, osteomata resemble more or less accu- 
rately bone tissue. They vary, however, in different areas, and mixtures 
of cartilage with bony tissue are frequent. Secondary degenerative 
changes (softening) may occur, and association with tumors of other 
character are not infrequent (chondroma, myxoma, fibroma, sarcoma). 




PROGRESSIVE TISSUE CHANGES 



181 



Nature. — These growths are eminently benign, slow of growth, do 
not recur, and do not give metastasis. Their situation sometimes makes 
them troublesome or dangerous. 

Angiomata 

This name is given to tumors the chief part of which is made up of 
vessels with a relatively small amount of supporting tissue. It is by 
growth of new vessels or increase of tortuosity of those existing that 
these tumors grow. The interstitial tissue may undergo change, but 
the principal feature is vessel sprouting. 1 

LYMPHANGIOMA 

A lymphangioma is a tumor composed of dilated lymph-vessels 
or lymph-spaces, more frequently the latter. It is difficult to separate 
dilatations of lymphatic channels due to obstruction from hyperplastic 
processes. Congenital enlargements of certain parts are met with 
which seem entirely dependent upon the abnormal development of the 
lymph-spaces. These constitute the condition called elephantiasis 
congenita mollis, in which the subcutaneous tissues are boggy or edem- 
atous, and even distinct cystic formations occur. Congenital cystic 
hygroma is an instance of dilatation of the lymph-spaces. Congenital 
enlargement of the tongue, termed macroglossia; of the lips, macrocheilia; 
and of the skin, ncevus lymphaticus, are other instances of the same 
process. In all of these, in addition to the dilatation of the lymphatic 
spaces, a marked proliferation of the connective tissues as well as the 
muscle (in the case of the tongue) is striking; but the process, in all 
probability, originates as a dilatation of the lymph-spaces. The term 
lymphangioma cavernosum has been suggested for these cases of dila- 
tation of the lymph-spaces. On staining with silver-salts the endo- 
thelial lining of the spaces may be readily demonstrated. Actual 
enlargement and varicosity of existing lymphatic vessels may occur, 
but is extremely rare in the form of circumscribed growths; it is met 
with more frequently in association with general processes, such as 
elephantiasis. The bursting of dilated lymphatics may lead to lym- 
phorrhea or external discharge of lymph when the process involves 
the skin, or to effusions of lymphatic character when the serous 
cavities are involved. Chylous pericarditis, pleuritis, and ascites are 
thus produced. Rupture of dilated lymphatics along the urinary tract 
(kidney or bladder) occasions chyluria. Lymphangioma is a benign 
process in the pathological sense. This classification is here limited to 
those tumors in which vessel change is the only feature, growths arising 
from lining or covering membranes being placed among the endothelio- 
mata. 

1 It is maintained by some that these are not true tumors, as they have no power of 
independent growth and keep pace with the body growth by reason of obstruction or an 
error of tissue resistance. The term "hamartoma" has been applied to them. 



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A TEXT-BOOK OF PATHOLOGY 



HEMANGIOMA 

Definition. — A hemangioma, or angioma, as it is more fre- 
quently called, is a tumor-like formation composed principally of 
blood-vessels. Two varieties may be described, that which simulates 
merely distended capillaries and veins (angioma telangiectaticum) , and 
that in which there are enlarged spaces lined with endothelium (angioma 
cavernosum or cavemoma). In many tumors the blood-vessels are 
somewhat enlarged; these are spoken of as telangiectatic tumors. 

Etiology. — Congenital malformation certainly plays some part 
in some cases, as the frequency of hemangiomata in the newborn and 
particularly at the junction of the branchial arches would indicate. 
Injury, however, and mechanical causes generally also play a part, and 
pre-existing disease, particularly fibroid inflammatory processes, may 
contribute to the subsequent dilatation and proliferation of the vessels 
(see below). 

Appearance and Seats. — The angioma telangiectaticum may 
consist merely of delicate capillaries and arterioles, and in this case 
a bright red color is observed. The tumor appears as a spot on the 
surface of the skin, more or less sharply outlined from the surrounding 
tissue. It is not elevated and has the same consistency as the healthy 
parts. Usually it occurs as a multiple condition, and the larger are often 
surrounded by smaller spots. The skin is the favorite seat; but the sub- 
cutaneous adipose tissue and sometimes the mucous membranes are 
involved. Less commonly larger (venous) channels occur in the tumor, 
when a dark red color is observed (port-wine stains). 

If a circumscribed portion of the circulation is uniformly involved, 
the vessels thicken and elongate, and a peculiar form of hemangioma 
results. In these cases the arteries are greatly thickened and tortuous, 
and form bunches under the skin, suggesting to palpation a bundle of 
earth-worms; while the surface of the skin presents peculiar irregular ele- 
vations without, of necessity, any change of color (aneurysma racemosum 
seu cirsoideum) . This is not infrequent in the scalp. A similar condi- 
tion of the vessels is observed in the varicosity of the legs, labia, or other 
parts. It is most frequent in the hemorrhoidal veins, constituting the 
ordinary hemorrhoids. (These conditions do not strictly constitute 
tumors and will be more fully described in discussing the diseases of the 
vessels.) 

Cavernous angiomata present themselves as more distinctly tumor- 
like formations of dark venous color, involving the skin or subcutaneous 
tissues, the retrobulbar tissue of the eye, the mucous membranes of the 
nose or pharynx, and certain organs, as the mammae, the kidney, the 
spleen, but particularly the liver. Like the other variety, they may be 
congenital, but more frequently arise in later life, especially that of the 
liver, which is most common in old persons. The appearance is that of 
a more circumscribed tumor, sometimes showing a distinct capsule and 
varying in consistency with the degree of distention of the blood-spaces. 
In the skin it projects slightly from the surface (ncevus prominens). 



PROGRESSIVE TISSUE CHANGES 



183 



Structure. — The definition explains the structure in general. 
The blood-vessels of telangiectatic angiomata may be simply dilated 
capillaries with a lining of endothelium and a fibrous outer coating. 
More commonly the vessels are considerably thickened and held together 
by a reticular connective tissue. In rare instances the vessels are so 
closely packed and the walls so thickened that when the blood is re- 
moved the appearance is not unlike that of the tubules of a sweat-gland. 
The congeries of vessels of a telangiectatic angioma represents the 
elongated and tortuous vessels of the affected area, and also new-formed 
vessels originating from the former. The only connection of the angioma 
with the general circulation is through one or a few afferent arterioles 
and efferent veins. The growth is not merely an enlargement of pre- 
existing vessels, but an actual new formation. 




Fig. 57. — Cavernous angioma (Warren). 



The cavernous angiomata present large spaces lined with endothelial 
cells (Fig. 57). Between these spaces are parallel fibers of connective 
tissue which form the framework of the tumor. In cases involving the 
liver the proper substance of this organ disappears completely, leaving 
only anastomosing spaces with a fibrous framework. Virchow taught 
that the fibrous process was primary, and by traction and pressure 
gradually induced dilatation of the vessels and atrophy of the liver sub- 
stance. Some of the more recent writers believe that the dilatation 
of the vessels is the primary condition. The capsule sometimes found 
surrounding the cavernous angioma is certainly a secondary formation. 

Angiomata of the skin may enclose the hair-follicles and sweat- 
glands; those of the subcutaneous tissue frequently show areas rich in 



184 



A TEXT-BOOK OF PATHOLOGY 



fatty tissue (angiolipoma) ; secondary angiomatous change of tumors is 
probably the result of dilatation of the pre-existing or new-formed ves- 
sels. Sometimes secondary change may occur in the connective tissue 
of the vessels of an angioma, as in the plexiform angiosarcomata, in which 
the blood-vessels are surrounded by ensheathing sarcoma-cells (see Fig. 
57). Certain cylindromata have the same origin. 

Nature. — Angioma is essentially benign, and may continue through 
life without enlarging. Hemorrhage and inflammatory or necrotic 
changes are its dangerous consequences. 

LYMPHADENOMA 

Definition. — This term is here used to designate a more or less 
malignant form of new growth affecting the lymphatic glands or other 
lymphadenoid tissues, and having the structure of lymphatic tissue. 
From a clinical and anatomical standpoint the manifestations of this 
condition are manifold, but histologically they have the same origin. 
They all arise from the lymphoblast, the endothelia, or both. Thus in 
the varieties lymphosarcoma and Hodgkin's disease the younger cells, 
or those nearer the parent cell, predominate, while in lymphoma and 
lymphatic leukemia the last stages of the lymphocyte series are more 
numerous. We shall consider under this heading the hyperplasias of 
lymph-tissue giving rise to tumors, leaving for the chapter on the Blood 
the leukemias, whose histogenesis is the same. (For discussion of 
Tumors of Lymph-glands, see p. 461.) 

There are several grades of lymphomatous disease, starting with 
simple lymphoma of nearly typical lymph-tissue structure and ending 
with true sarcoma of lymph-nodes, which, of course, are of the small 
round-cell type. To differentiate between closely related conditions is 
a problem of great difficulty and questionable utility. There are dis- 
cussed here simple lymphoma, lymphomatosis, and Hodgkin's disease, 
conditions affecting the lymphocyte-producing organs, yet, curiously 
enough, failing to produce any marked alteration of lymphocyte content 
in the blood. With the exception of simple lymphoma, a rare, probably 
hyperplastic or inflammatory condition, these diseases seem to be sys- 
temic, since change in one locality is followed by lymphoid overgrowth 
almost universally in the body. 

Etiology. — There are cases of infectious enlargement of the glands and 
traumatic swellings that cannot be clearly distinguished from lymph- 
adenoma. In some cases even the clinical course is the same and a sepa- 
ration seems impossible. For example, the glands in a number of in- 
stances of Hodgkin's disease (as far as the clinician can establish this 
diagnosis) have been found to contain tubercle bacilli. We must con- 
clude that general lymphatic tuberculosis may occur in clinical forms 
indistinguishable from Hodgkin's disease, but cannot assert that this 
establishes the pathological identity. Tubercle bacilli have been dis- 
covered in some cases diagnosed as lymphomatosis (Sternberg and 
Gross), and in other cases where they were absent, Frankel and Much 



PROGRESSIVE TISSUE CHANGES 



185 



have found Gram-positive rods or coccus-like bodies which Much claims 
to have shown are tubercle bacilli having lost acid-fast properties. The 
large number of eosinophiles in the gland speaks rather against the 
tuberculous nature of the growth. The presence of tubercle bacilli may, 
furthermore, be explained as sometimes the result of secondary infec- 
tion. In a number of well-studied cases the absence of tubercle bacilli 
has been proved by the inoculation of animals. 

Various micrococci and bacilli have been discovered in glands from 
cases of Hodgkin's disease. This condition has lately been ascribed 
to a pseudodiphtheria bacillus which can be isolated from the glands 
by a special technic. Some have claimed to have reproduced the dis- 
ease in monkeys by injection of the bacteria, but this must be corrob- 
orated. Others claim good results in treatment of clinical cases by the 
use of bacterins of this newly discovered organism. It is important, 
however, to note that similar diphtheroid organisms have been iso- 
lated from other diseases of lymphatic glands. In a few instances 
bodies resembling protozoa have been discovered. 

Appearance and Seats. — Lymphadenomata present themselves 
as enlargements of the lymphatic glands of a single group or,, more com- 
monly, of a number of groups in different parts of the body. All of the 
glands of the group may be involved, or only a few. The individual 
glands retain their shape, as there is usually no tendency to extension 
beyond the capsule of the gland. In exceptional cases, however, the 
process is of a more infiltrating kind and the capsule is penetrated or 
destroyed. These instances merit the special term "lymphosarcoma." 

Lymphadenomata may be soft or hard, according to the amount 
of connective tissue and the denseness of the cellular infiltration and 
proliferation. On section, the tumors are found to be grayish or whit- 
ish in appearance, and exceptionally may show slight areas of necrosis 
or softening. Extensive softening is exceedingly rare. The individual 
glands of the group may be clearly distinct, or may be fused together 
by interglandular connective-tissue overgrowth or by the penetration 
of the lymphadenomatous process through the capsule. 

When superficial lymphatic groups are involved, tumors of various 
sizes are produced, and project as knobby or rounded enlargements be- 
neath the skin. The latter is freely movable over the tumor unless the 
growth has penetrated the capsule or secondary inflammatory changes 
have occurred. In the case of internal glands large intrathoracic or ab- 
dominal growths may be formed, and may exercise destructive com- 
pression of vital parts. 

Similar lymphadenomatous growths may spring from the lymphatic 
tissues of the gastro-intestinal tract — tonsils, lymphatic follicles of gas- 
tric and intestinal mucosa. 

Sometimes the primary growth seems to begin in the thymus gland 
or its remnant (Fig. 58). Tumors of considerable size are produced in 
these cases, and their origin is recognized by their shape (two lateral 
parts united by a sort of isthmus) and by the absence of the appearance 
of a conglomeration of glands. In these cases the adjacent glands 



186 



A TEXT-BOOK OF PATHOLOGY 



and, later, more distant groups are involved. Lymphadenoma may be 
confined to the glands, but frequently extends to the solid organs by 
metastasis. The spleen, liver, and kidneys are the organs most fre- 
quently affected. They become enlarged and indurated, and on section 
show light colored areas of lymphadenoid tissue. Similar "lymphoid 
infiltration" may be seen in the heart, lungs, or other parts. 

Lymphadenoma may affect the bone-marrow secondarily and per- 
haps primarily. (Reference will be made to this under the title Mye- 
loma.) Sometimes the tumors have a yellow or green color and are 
called chloromata (q. v.). 



Fig. 58. — Lymphadenoma (lymphosarcoma) probably originating in remnant of thy- 
mus gland: the tumor covered the upper part of the heart like a hood. The illustration 
shows the tumor turned upward and exposing the pericardium on its under surface. 



Structure. — Histologically, the glands in the earlier stages show a 
hyperplasia of lymphadenoid tissue with predominance of small cells 
(lymphocytes). Later larger cells with pale nuclei make their appear- 
ance. Most of these are bizarre forms of the proliferating lymph-cells, 
while some are swollen endothelium from the sinuses. They may 
enlarge to form mononuclear or polynuclear giant-cells, the nuclei 
dividing by amitosis. Sometimes large areas of nucleated protoplasm 
(syncitial tissue) are observed. At this time the gland section is gener- 
ally homogeneous in arrangement, all parts actively growing, and the 
architecture of follicles, cords, and sinuses is largely obliterated. Coin- 
cidently with the appearance of these epithelioid and giant-cells there 
is formed a reticular fibrous network which increases with the age of the 
process until the gland becomes quite indurated. A somewhat char- 





PROGRESSIVE TISSUE CHANGES 



187 



acteristic, though not constant, feature of the histology is the presence of 
numerous eosinophile leukocytes scattered through the tissue or in small 
masses. These may be mononuclear or polymorphonuclear. Plasma- 
cells and mast-cells may be present, but are not characteristic. 

In the rapidly growing form, commonly called "lymphosarcoma," 
the cells, while still near the parent type, are more uniform in size and 
shape, more deeply staining, more active in proliferation, and there are 
fewer endothelioid and eosinophilic cells than in the Hodgkin's type. 
The clinical history may be the same, and one cannot now state the 
reasons for these differences, unless they be stages of the same process, 
a view held by some observers. 

The above description leads one from the hyperplastic lymph-gland 
to the fully developed adenoma, made up of imperfectly differentiated 
cells. It is well to emphasize that in Hodgkin's disease the picture is 
dominated by large endothelioid cells in group arrangement mixed with 
groups of small lymphoid cells; many eosinophils are to be found. 
There is a fine fibrosis running through the tissue. Focal necroses are 
common. 

The spleen may show similar changes, beginning in the Malpighian 
bodies, but in many cases is affected in but slight degree or not at all. 

The bone-marrow presents a picture of proliferation of myelocytes. 

The liver, kidneys, lungs, gastro-intestinal mucosa, and other tissues 
may be extensively involved, presenting new, formations of the lym- 
phoid cells similar to those in the glands and originating from the 
lymphoid masses normal to these parts. These lesions were formerly re- 
garded by most authorities as simple metastases, but are now thought by 
many to be proliferations of existing lymphoid tissue. Some, as Ribbert, 
hold that they are metastatic and are due to proliferation of metastatic 
cells, which, however, are attracted to pre-existing lymphoid collections 
by a species of chemotaxis that seems to invite the deposit of cells in 
areas where similar cells exist. 

The occasional perforation by the growths of small blood-vessels 
with proliferation within the vessels is an argument in favor of the 
neoplastic nature of the process. 

Nature. — Lymphadenoma is variably malignant. In a small pro- 
portion of the cases this malignancy is of local character — that is, the 
growth tends to invade the neighboring parts. In most instances there 
is rather a tendency to general involvement of the lymphatic system, 
with secondary growths in various organs. To cases of this kind the 
terms "Hodgkin's disease," "pseudoleukemia," and "adenia" have been 
given. These cases present themselves in the form of a progressive ane- 
mia (lymphatic anemia — Wilks), often with irregularly relapsing fever 
(chronic relapsing fever — Epstein), and especially with lymphadenoma- 
tous tumors in the superficial or deep lymphatic groups (axillary, 
cervical, inguinal, mediastinal, or abdominal). The disease progresses 
more or less rapidly, and terminates in death from cachexia and exhaus- 
tion in from one to three years. Occasionally the course is rapid, re- 
peated hemorrhages or purpura may occur, and a fatal termination 



188 



A TEXT-BOOK OP PATHOLOGY 



is reached in a few weeks or months. The whole course of the disease is 
in these cases suggestive of an infectious process. The chronic cases 
may be infectious or due to some form of toxemia, but are at present 
more appropriately considered under the head of Tumors. 

The relation of Hodgkin's disease and leukemia, especially the 
lymphatic type, is certainly very close. The glandular tumors and the 
secondary changes in the organs are somewhat similar, excepting that 
the lymphatic glands are more prominently involved in ordinary lymph- 
adenoma and the marrow changes more striking in leukemia. The 
striking difference is found in the blood. In leukemia there is marked 
and characteristic leukocytosis; in the other condition this is absent. 
Many cases have, however, been observed in which Hodgkin's disease 
has apparently become leukemia; and some authors do not hesitate to 
speak of the two diseases as identical and representing merely two 
stages of a common affection. According to this view, we might 
classify different cases as either leukemic or aleukemic lymphadenomata. 
The blood in aleukemic cases shows more or less pronounced reduc- 
tion in the number of red cells, and a normal, reduced, occasionally a 
moderately increased, number of leukocytes. The small mononuclear 
leukocytes are sometimes in relative excess. In acute cases nucleated 
red cells may be found. 

The causes and nature of the irregular fever are uncertain. It may 
be due to an infectious cause, or may be the result of breaking up of 
leukocytes and liberation of ferments. 

Multiple Myeloma. — This growth affects the sternum, ribs, vertebrae, 
skull, and, less frequently, other bones. The tumor at first suggests a 
hyperplastic condition of the marrow; later the substance of the bone is 
replaced by the growth, which may finally break through the shell of 
bone covering it and invade the soft tissues. Metastasis is very rare. 
The growth has a mottled grayish and reddish appearance and is rather 
soft. Microscopically it is composed of small round cells and a vascular 
network of thin-walled vessels. The cells resemble small myelocytes or, 
possibly in some cases, plasma-cells. There is also a type, the lymphoid, 
in which lymph-cells predominate. Bence-Jones albumose is found in 
the urine in cases of myeloma. 

Chloroma is the name given to the greenish solid hyperplasias of the 
bone-marrow growing from the premyelocytes and owing their color to 
an abundance of lipochromes. This color vanishes on exposure to air. 
The tumor is probably merely a condensation of hyperplastic marrow 
in cases of myelogenous leukemia, as certain differentiations of the com- 
ponent cells into granular myelocytes, the occurrence of typical leu- 
kemic metastases, and the development of an enzyme acting in alkaline 
medium, all point in the direction of a hyperplasia of leukocytic ele- 
ments. The superficial resemblance of the premyelocytes and large 
lymphatic cells has led to the erroneous opinion that chloroma was a 
lymphosarcoma, so that the names "myeloid" and "lymphoid" have 
been given to those cases in which respectively the granular and non- 
granular myelocytes have predominated. The similarity of the latter 



PROGRESSIVE TISSUE CHANGES 



189 



and large lymphatic cells is marked, but all the cells of chloroma are 
now thought to be derived from the myelocytic series. 

SARCOMA 

Definition. — The term "sarcoma" is applied to tumors composed 
of connective-tissue cells with very little intercellular substance. It 
is often said that sarcoma-cells resemble those of embryonal connective 
tissue; properly speaking, they may be likened to the ordinary con- 
nective-tissue cell falling short of complete development — that is, no 
formation of fibrous intercellular substance, but a great tendency to 
continuous cell proliferation. 

Etiology. — Of all the tumors, sarcoma furnishes the best ground for 
Cohnheim's theory. Its frequent occurrence in young persons, the 
relation of melanosarcomata to congenital pigment-spots of the skin, 
and the sarcomatous mixed tumors of the parotid and testis were cited 
by Cohnheim among the evidences pointing to a congenital origin. 
Traumatism and inflammation certainly play some part, either in stimu- 
lating sudden growth of a latent sarcoma or in developing a lesion from 
which sarcoma springs. The parasitic theory has gained many adher- 
ents in recent years, though no specific organism has been demonstrated. 
Experiments at implantation of the disease in animals have been par- 
tially successful, but do not establish an infectious character, as has been 
shown in preceding pages. It is not improbable that certain lympho- 
sarcomata may be due to the action of bacteria. 

Appearances. — Sarcomata are generally more or less rounded 
tumors, often enclosed by a limiting reactive inflammation of the neigh- 
boring tissues; they may, however, be irregular, infiltrating, and, 
therefore, unencapsulated. The growth of sarcomata is from the tumor 
cells themselves. The tumor spreads into the surrounding tissue and 
absorbs it, probably only retaining such connective tissue as it requires. 
A true fibrous capsule, 'made by the tumor and within which it 
grows, does not occur in sarcomata. Some forms appear on surfaces, 
spreading as flat elevations more or less irregular in outline. The 
consistency is soft or hard according to the number of cells and the 
amount of intercellular substance, or according to the kind and amount 
of associated tissue (myxomatous, chondromatous) . Typical sarcoma, 
as the name implies (odp£, flesh), is flesh-like in consistency, and 
frequently, on section, the color is pink or of a flesh-tint. Many of the 
sarcomata, however, are quite white or gray, and a whitish liquid 
exudes from the surface on section. 

Dilatation of the blood-vessels may cause a decidedly hemorrhagic 
appearance, and actual hemorrhages may take place, causing blood- 
cysts or, subsequently, serous cysts. Other degenerative changes, 
such as necrosis, mucoid change, and simple liquefaction necrosis, may 
render sarcomata soft and often cystic. Sarcomata of glandular organs 
like the breast may present a cystic appearance in consequence of 
compression, and subsequent dilatation of the glandular ducts and 
acini. 



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A TEXT-BOOK OF PATHOLOGY 



Angiosarcomata (the variety in which sarcoma-cells spring from 
the adventitia of blood-vessels) present themselves as more or less 
irregular growths, frequently flattened and branching when the surfaces 
of organs are involved. 

Secondary sarcomata are nodular in character and nearly always 
present a capsule if the size is at all considerable (Fig. 59). They are 
usually white or pinkish; rather firm on section, but with a tendency to 
central necrosis or softening. In some cases almost every part of the 

body may be studded with 
minute white spots scarcely 
distinguishable from miliary 
tubercles. This condition is 
called sarcomatosis. 

Seats. — Sarcomata spring 
from pre-existing connective tis- 
sues, such as the subcutaneous, 
intermuscular, periosteal, or 
tendinous tissues; bone, cartil- 
age, fat, lymphatic glands, the 
submucous and serous surfaces. 
They may arise in the internal 
organs: kidney, liver, spleen, 
thyroid glands, testis. The in- 
dividual seats will be further 
considered under the different 
forms. 

Structure. — The sarcoma- 
cell is rounded, cylindrical, spin- 
dle shaped, or of polymorphous 
forms, the latter usually being 
larger than the round or spin- 
dle forms. The large number 
of cells in comparison with the 
amount of intercellular sub- 
stance is always conspicuous. 
The cells themselves contain rather large nuclei of a somewhat vesicular 
appearance, though sometimes quite granular and hyperchromatic. 
In rapidly growing tumors karyokinetic figures may be very abun- 
dant; less frequently the cells show evidence of direct division of the 
nuclei. Nuclear degenerations (karyorrhexis, karyolysis, and hyper- 
chromatosis) are frequent, and doubtless cause some of the appear- 
ances supposed to be protozoa. The arrangement of the cells in sarco- 
mata is usually very irregular; in some cases, however, particularly in 
spindle-celled sarcomata, the cells lie in fasciculi or parallel columns. 
These are the alveolar sarcomata. The intercellular substance consists 
of a homogeneous matrix with a few fibers in the case of the spindle- 
celled variety, but with few if any in other cases. The cells may be 
all of one type, but more frequently different forms or shapes occur in 




Fig. 59. — Secondary sarcomata of the lung: 
the primary growth was attached to the 
pleura. 



PROGRESSIVE TISSUE CHANGES 



191 



the same tumor. Among the polymorphous forms of cells may be noted 
large flattened cells resembling endothelial plates and giant-cells resem- 
bling myeloplaques. (These forms will be discussed under the headings 
Endothelioma and Giant-celled Sarcoma.) 

When grown in serum outside the body, sarcoma cells at first multi- 
ply more rapidly than normal ones, but soon lose this power. Irregular 
mitoses are seen, but direct division is not. 

The blood-vessels of sarcoma are usually channels lined with a single 
endothelial coat (see Fig. 61), but there may be more fully developed 
vessels. There is growth of these imperfectly formed vessels, following, 
in general, the laws of new capillary development. In some cases the 
vascular network is very conspicuous and forms the skeleton of the 
tumor, the sarcoma-cells being ranged round the vessels in the form of 
mantles and probably springing from the adventitia. In spreading, 
sarcoma shows a tendency to follow vessels. It has no lymphatics and 
only such nerves as it encloses in its growth. Secondary changes may 
occur in the cellular masses surrounding the vessels, and peculiar forms 
of tumors thus result. (See Cylindroma.) 

The general architecture of a sarcoma has a decided influence upon 
its character. The round-cell tumors are usually of rapid growth and 
the small round-cell type of the greatest malignancy among the simple 
sarcomata. The soft loose-textured ones are usually most malignant. 

Combinations of sarcoma with other forms of tumors are not rare. 
All grades between the true sarcoma and the fibroma may be met with, 
and it is difficult to draw a line of distinction. Wherever a tendency to 
cellular proliferation is conspicuous and the formation of fibroblastic 
cells with elongated fibrous projections is not conspicuous, it is warranted 
to record the tumor as sarcomatous. Primary fibromata may become 
sarcomatous, and sarcomatous tumors perhaps at times become more 
benign by fibromatous transformation. Combinations with chondroma, 
osteoma, myxoma, and other connective-tissue tumors; with adenoma, 
rhabdomyoma, and fibromyoma are not infrequent. More rarely 
the fibrous tissue of the benign tumors may undergo sarcomatous 
change. 

The structure of individual forms of sarcoma will be separately 
considered. Names have been applied to the different forms which 
describe the micro-anatomy, and in a sense are instructive in suggesting 
the relative activity and possible nature of the growth. It must not 
be forgotten, however, that round- and spindle-cell sarcomata both de- 
scend from the same parent cell and may be phases of differentiation. 

Nature. — Sarcoma is essentially malignant. It tends to recur 
after removal; it affects the general health of the patient, and metastasis 
is frequent. Metastasis occurs through the circulation chiefly, but 
may spread through the lymphatics. The degree of malignancy varies 
greatly. The small round-celled and melanotic varieties are the most 
dangerous. Some forms, as the giant-celled and the fibrosarcomata, are 
comparatively benign. The relatively benign form of tumor, called 
recurrent fibroid tumor by Paget, is, in reality, a fibrosarcoma. The 



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A TEXT-BOOK OF PATHOLOGY 



growth of sarcomata is usually rather rapid, but shows a tendency to 
irregularity, and may become very rapid in consequence of irritation. 

Sarcomata are injurious to the general health in some obscure way. 
The evidence of this is the anemia and leukocytosis and the irregular 
fever observed in various cases. The anemia may be trivial or severe, 
and may become extreme. Leukocytosis is frequent, but rarely marked. 
The polymorphous elements may be specially increased, but we have 
found the lymphocytes excessive in a number of cases. Irregular fever 
is often noted in lymphosarcoma and sarcomatosis. Necrotic change 
may increase the tendency to fever. The exact influence of sarcoma on 
metabolism is unknown. 

Spindle-celled Sarcoma 

This form may consist of either large or small spindle-shaped cells 
with attenuated and sometimes branching extremities, and a spindle- 
shaped nucleus in the small cell variety, while the large cells have an 
oval, bladder-like nucleus (Fig. 60). Angular or stellate cells are not 




Fig. 60. — Cells from a large spindle-celled sarcoma (Ziegler). 



infrequent. The cells may be ranged in parallel columns, so that the 
tissue becomes quite compact; and fasciculi of such cell masses may run 
in different directions, interlacing, and thus giving the section a fibrous 
appearance. In some cases the cells present no definite arrangement. 
Spindle-celled sarcomata are harder than the round-celled varieties 
and usually more grayish or flesh colored. They may be quite soft and 
white or degenerated and cystic. 

The amount of intercellular substance in some cases, particularly of 
the small cell type, is quite considerable, and the term "fibrosarcoma" 
may be justified. The intercellular fibrils are of the fibroglia type and 
are indistinguishable from those of fibromata. It is very difficult some- 
times to decide whether the tumor is sarcomatous or purely fibromatous. 
The large cell type is more cellular. 

Spindle-celled sarcomata occur in the dense connective tissue of the 
periosteum, tendons, and fasciae; less frequently, in the softer tissues. 
They are slow of growth, relatively benign, some cases showing no tend- 
ency to metastasis, though recurring after removal. 



PROGRESSIVE TISSUE CHANGES 



193 



Round-celled Sarcoma 

Sarcomata may be composed almost entirely of spherical or round 
cells, small or large in size. The designations "small" and "large round- 
celled sarcomata" are used, but do not really define separate varieties. 
The round cells when small resemble those of lymphatic organs. There 
is little intercellular substance. The blood-vessels may be quite large 



Fig. 61. 



-Small round-celled sarcoma: in the center is seen a blood-vessel with its wall 
of endothelium. 




and hemorrhages with secondary changes may occur (Fig. 61). The 
larger cells contain relatively more protoplasm, frequently several nuclei, 
and not rarely different forms of cells (spindle shaped and polymorphous) 
are associated. 

The naked-eye appearances of round-celled sarcomata are usually 
quite characteristic. They are milky-white, gray, or pink in color; 




sometimes quite soft or cheesy in the center, and a milky liquid exudes. 
Cystic changes and even calcification may occur in the center. The 
small-celled variety is, as a rule, softer than the larger, though both are 
soft. 

Round-celled sarcomata are always malignant, the small-celled form 
being perhaps the most malignant of all varieties. 

13 



194 



A TEXT-BOOK OF PATHOLOGY 



Lymphosarcoma is a variety of round-celled sarcoma. The ap- 
pearance is the same as that of the other forms, but, microscopically, 
a close resemblance of structure with that seen in lymphatic glands is 
discovered. The principal characteristic is the reticulum or stroma 
formed by branching stellate cells united by their prolongations. In 
the meshes of this reticulum lie lymphoid round cells (Fig. 62). The 
stroma may not be plainly visible unless sections are shaken to dislodge 
the cells from the reticulum. The lymphosarcoma cell has a rather 
large round eccentric nucleus surrounded by a basophilic granular 
protoplasm. The distinctions of lymphosarcoma from lymphadenoma 
have been discussed under the latter heading. The principal feature of 
differentiation is the tendency of lymphosarcomata to extend beyond 
the normal limitations of the gland or other structures in which they 
originate, whereas lymphadenomata are confined by the glandular 
capsule. 




Fig. 63. — Alveolar sarcoma (Warren). 



Alveolar sarcoma is a subvariety of round-celled sarcoma, though 
there are always spindle cells as well. It is distinguished by the occur- 
rence of structures suggesting acini and filled with large round cells 
having a more or less decided epithelioid appearance. The stroma 
forming the acini is composed largely of spindle-shaped cells with a 
certain amount of fibrillar intercellular substance (Fig. 63). The blood- 
vessels supplying the tumors traverse these trabecular. The round cells 
within the alveoli may vary greatly in size, though they are usually 
large. The macroscopical appearance is not specially distinctive; many 
of the cases, however, are pigmented (see below). Alveolar sarcoma is 
most frequent in the skin, where it springs from moles and warts. It 
may also occur in the lymphatic glands, the serous membranes, and 
other parts. 

In some cases the alveolar appearance of the sarcoma is due to the 
fact that the sarcomatous proliferation has occurred in the adventitia 



PROGRESSIVE TISSUE CHANGES 



195 



of blood-vessels, forming a plexus. In this way the meshes of the vascu- 
lar plexus become filled with round cells and the alveolar appearance 
results. In other cases the alveolar character is due to the occurrence 
of sarcomatous foci of circumscribed character in a connective tissue. 
These in their growth push the connective-tissue elements aside and 
thus form alveolar structures. 

Giant-celled Sarcoma 

This variety is characterized by the presence of large multinuclear 
cells resembling exactly the myeloplaques of bone. The remaining 
portions of the tumor may be spindle celled or round celled; perhaps 
more frequently round and spindle cells are associated. The giant- 
cells are often exceedingly large and contain several or many nuclei in 




Fig. 64. — Giant-celled sarcoma (Warren). 



the center of the cell (Fig. 64). The formation of these cells is most 
likely due to rapid nuclear multiplication. In some cases they would 
seem to be caused by obliteration and transformation of capillary 
blood-vessels; but the theory that they result from a fusion of cells 
seems unwarranted. Ziegler and others maintain that the presence 
of giant-cells does not form an essential characteristic of a peculiar 
type of tumor, but that it is accidental, resulting from continued irri- 
tation. The occurrence of giant-cells in sarcomata of bones would then 
be explained by the constant irritation of the bony particles, while in 
other cases the presence of masses of blood-pigment in the sarcoma ac- 
counts for the development of giant-cells in the vicinity. This view is 
supported by considerable authority and seems reasonable. 

Giant-celled sarcomata occur most frequently about bone, and the 
terms osteosarcoma (a term to be avoided for this growth) and myeloid 



196 



A TEXT-BOOK OF PATHOLOGY 



sarcoma have been given in consequence. They may, however, occur 
in other situations. Their nature is usually benign, metastasis being 
rare. 

The giant-celled sarcoma of bone is usually rather slow in growth, 
and gives rise to hard and irregular tumors, firmly attached to the bone 
structures. It may begin within the bone as a myelogenous form (Fig. 
65) or from the periosteum. Secondary myxomatous or other change 
may cause more or less softening. The bone most frequently in- 
volved is the maxilla, the tumor known as epulis (sarcoma springing 



> 




Fig. 65. — Myelogenous osteosarcoma of the tibia (modified from Kast and Rumpel). 

from the gums or alveolar processes) being generally a giant-celled 
sarcoma. 

The true osteosarcoma is a more definitely neoplastic process involving 
a growth of young, irregular connective-tissue cells with imperfect bone 
formation. There may be giant-cells, but they do not dominate the 
field as in the tumor just described. There may be several kinds of cells 
in the osteosarcoma. Such tumors are definitely progressive and malig- 
nant, as against the less active giant-cell myeloid tumor above. With 
their growth they absorb bony tissue, and lay down new atypical osseoid 
material. They may be cartilaginous, or chondro-osteosarcomatous, or 
any combination of bone, cartilage, and sarcoma. The various kinds 
of cells found in sections of this tumor indicate alterations in cells 
natural to bone, either taking part in the sarcoma or being modified 
by the new growth. Thus one may find cells resembling adult bone 



PROGRESSIVE TISSUE CHANGES 



197 



or cartilage cells and sarcoma-cells. When growing within a bone 
these tumors thin the shaft so that the thinned-out bone gives the 




Fig. 66. — Bony structure of osteosarcoma of tibia. 

"egg-shell crackle." The more cellular and less bony, the more malig- 
nant is the tumor, and vice versa (Fig. 66). 

Melanosarcoma 

Melanosarcoma, melanoma, chromatophoroma, or pigmented sar- 
coma is a form in which the tumor presents a dark color on account of 
the presence of black or brown pigment. The latter, according to care- 
ful chemical studies of Berdez and Nencki, contains no iron, and is, 
therefore, not a simple blood-pigment, but melanin, a product of cell 
metabolism. Iron-containing pigment has been found in some tumors, 
and sometimes in true melanosarcomata, being found outside the cells 
and probably accidental, the result of hemorrhagic extravasations. 
The true melanin pigmentation occurs in the cells, in the cellular pro- 
longations, or the intercellular fibrils. It is most frequently present in 



198 



A TEXT-BOOK OF PATHOLOGY 



the form of brownish-black granular matter, or may occur as a diffuse 
stain. 

Melanosarcoma most commonly arises in the skin, especially in pig- 
mented moles or warts, in the choroid coat of the eye, or in the pia 
mater. The growth is found to consist of cells of various shapes, some- 
times round or irregular, sometimes spindle shaped, but there is a very 
constant tendency, especially in the pigmented sarcomata of the skin 
springing from warts, to assume an alveolar arrangement. In these, 
the cells around the periphery of the alveoli are more or less spindle 
shaped, while those in the center are large, irregular, or rounded cells, 
sometimes epithelium-like. Melanotic sarcomata of the choroid are 

composed very largely of cells hav- 
ing an elongated character with 
drawn out extremities. These re- 
semble the normal pigment cells of 
the choroid coat. 

Melanosarcoma is extremely ma- 
lignant, recurring when removed and 
frequently causing extensive metas- 
tasis (Fig. 67). The latter involves 
the local lymphatic glands in the first 
place, but later various organs, es- 
pecially the liver. The metastases 
may be of the same structure as 
the original growth, but sometimes 
non-pigmented metastatic growths 
occur in association with the pig- 
mented ones. Occasionally the sec- 
ondary deposits are more pigmented 
than the primary growths. The 
melanoma originates from the pig- 
ment-containing cells or chromato- 
phores of the part in which they 
originate. In the skin these are 
found in close association with the 
lower layers of the epidermis, and 
some authors have insisted that they are essentially epithelial in origin and 
that the tumors should, therefore, be considered as carcinomata. There 
is, however, considerable ground for believing that the chromatophores 
are invariably connective-tissue cells. Melanosarcoma is a definite 
growth and not merely a sarcoma that happens to be pigmented. 




Fig. 67. — Metastatic melanosarcoma 
of lung, showing pigmented and non-pig- 
mented nodules (from a specimen in the 
possession of Dr. Allen J. Smith). 



MIXED TUMORS 



All forms of connective-tissue tumors may be associated one with 
another; association of several forms are known as mixed tumors. Very 
frequently there is more or less sarcomatous tissue in such growths. 
With this will be found myxomatous, fibromatous, chondromatous, or 



PLATE i 




Melanosarcoma. 



PROGRESSIVE TISSUE CHANGES 



199 



osteomatous elements. The various constituents of the tumor are 
arranged with no special order, but simply present themselves as masses 
of cells or intercellular substance of different forms combined to make 
a heterogeneous tissue. Among the frequent seats of such mixed tumors 
the parotid gland and the testicle are most important. A not infre- 
quent combination is that of sarcomatous and adenomatous tissue. 
Tumors of this character are supposed to develop from embryonal 
"rests," and are particulary common in the kidney, where they often 
reach large sizes. (See also Teratomata.) 




Fig. 68. — Mixed tumor of thyroid gland. 



Adrenal "rests" in the kidney give origin to the Grawitz tumor or 
hypernephroma, a tumor largely composed of cells resembling adrenal 
cells, arranged in adenomatous fashion. (See Tumors of Kidney.) 

Mycosis Fungoides 

Mycosis fungoides or granuloma fungoides is a pathological condition 
of the skin and subdermal structures, having certain resemblances to 
sarcoma and to some of the infectious inflammations. 

Etiology. — Very little is known regarding the causes of this disease. 
Various bacteria, principally micrococci, have been discovered in the 
lesions, but none of these has been shown to be pathogenic. A few 
observers have found bodies resembling protozoa; but.it is not certain 
that these were really animal organisms. 

Appearance. — The disease frequently presents distinct stages. 
First, the skin becomes somewhat swollen and red and presents eczema- 



200 



A TEXT-BOOK OF PATHOLOGY 



tous lesions. In some cases the appearance is that of an erysipelatous 
inflammation. In the next stage nodular elevations occur, and finally 
tumors of considerable size, sometimes as large as an orange, and more 
or less fungoid in appearance. Necrosis is frequent and watery or bloody 
liquid is discharged. The tumors may have an angry, red appearance, 
and have been likened to tomatoes. Rapid disappearance and reappear- 
ance of the tumors is a peculiar feature. 

Any part of the body may be affected, and usually the lesions are 
multiple. 

Structure. — Microscopically, the structure of the tumors is allied to 
that of lymphadenomata. There is a proliferation of connective-tissue 
cells about the blood-vessels and glands at the base of the papillae of the 
skin, forming a network or reticulum in which round (lymphoid) cells 
are embedded. The cells, however, may be irregular in form and size. 
Mitotic figures may be found. Early in the disease the new-formed cells 
degenerate considerably, but later proliferation predominates, and the 
tumor results. The epithelium covering the growth may be thinned 
to a single layer, or it may show thickening. In the latter case enlarged 
papillae dip down into the round-cell collections and the sections have 
somewhat the appearance of carcinoma. Epithelioid cells and giant- 
cells may occur. The tumors are poorly supplied with blood-vessels, 
and to this is attributed the tendency to central necrosis. Inflammatory 
'infiltration (polymorphous leukocytes) is not observed to any consider- 
able degree, excepting in the latter stages around and in the areas of 
necrosis. Mast-cells are often abundant. 

Associated Conditions. — In some cases enlargement of the lym- 
phatic glands, liver, and spleen has been observed, and has suggested 
the term pseudoleukemia cutis. Occasionally the blood presents leukemic 
characters. 

Nature. — The disease presents many resemblances to sarcoma or 
lymphadenoma, and it has frequently been described as multiple sarcoma 
of the skin. In other respects it is allied to the infectious inflammations, 
though there is much less evidence of true inflammatory infiltration than 
in these. The relationship to leukemia and pseudoleukemia is un- 
settled. 

Angiosarcoma 

The angiosarcomata are growths depending upon a proliferation of 
endothelium and an expression of the tendency of these cells to make new 
vessels. The tumors arising in lymph-channels are called lymphangio- 
endothelioma or lymphangioma, while those in blood-vessels are called 
hemangio-endothelioma, or simply angiosarcoma. In the second variety 
the sarcomatous proliferation may begin in the adventitious coat of 
blood-vessels (perithelioma) . 

Angiosarcomata are met with in the serous membranes, in the skin, 
and especially in the salivary glands. Very rarely they occur in other parts 
of the body. The tumor is, as a rule, quite vascular, but may not be 
strikingly so. Sometimes telangiectatic change in the blood-vessels is 



PROGRESSIVE TISSUE CHANGES 



201 



noted. Histologically these growths are characterized by round-celled 
masses surrounding the blood-vessels. The origin of the cells from the ad- 
ventitia may be evident or obscure. In cases in which a vascular network 
is involved and each vessel has a coating of sarcoma-cells a plexiform 
appearance or arrangement results (plexiform angiosarcoma). In other 
instances in which a network of vessels is involved the sarcoma-cells 
accumulate in the vascular meshes in the form of cell-nests, and thus 
give rise to an alveolar form (alveolar angiosarcoma). Such forms 
occur in sarcomata springing from moles or warts. They are prone to 
melanotic change. The endothelium of the vessel is also the point of 
origin of vascular sarcomata. The proliferation of the endothelium 
leads to increase in vessels, narrowing of the lumen by irregular fibrosis. 




Fig. 69. — Angiosarcoma with myxomatous degeneration (cylindroma) : the figure rep- 
resents one of the blood-vessels with the sarcomatous cells springing from its walls, and 
outside of these myxomatous tissue. 

Sometimes the original adventitia remains about the same size, but 
the lumen is filled with endothelium. 

The angiosarcomata are liable to degenerations, chiefly myxomatous 
(Fig. 69) and hyaline, and thus a certain proportion of the cases of cylin- 
droma (see below) have their origin. The blood-vessels may give way 
and hemorrhagic infiltration rasults. 

Angiosarcomata are, in a measure, benign, metastasis being very 
rare in the ordinary forms. The alveolar and melanotic varieties are 
highly malignant. 

Lymphangiomata are moist, gray, soft, spongy growths, commonest 
in the spleen. They are, however, quite rare. They consist of pro- 
liferated lymph-channels with well-marked swollen endothelial lining 
cells. 



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A TEXT-BOOK OF PATHOLOGY 



Cylindroma 

This term was originally applied by Billroth to tumors showing 
gelatinous masses or trabecular traversing their substance. Histologically 
different forms of growths may be distinguished. We deal here only 
with sarcomatous cylindromata. 

The latter may be simply sarcomata in which hyaline or myxoma- 
tous degeneration has occurred in more or less insular fashion, or in 
which sarcoma and myxoma are peculiarly combined. Nearly always 
there is some hyaline change with the myxomatous. In most cases it is 
the angiosarcomata that present this peculiar condition. The sarcoma- 
cells surrounding the blood-vessels become converted into hyalomyxo- 
matous tissue or cause the formation of this. There result branching 




Fig. 70. — Cylindroma showing pronounced hyaline degeneration of the walls of the blood- 
vessels. 

columns of hyalomyxomatous character traversing the sarcoma. In 
some cases the walls of the blood-vessels themselves may be the seat of 
hyaline change (Fig. 70), the proliferated sarcoma-cells surrounding the 
vessel being merely pushed aside. The term angiosarcomata myxoma- 
toses is given to these vascular forms. Cylindromata occur in the 
salivary glands, the brain, the lacrimal* glands, and rarely in the sub- 
cutaneous tissues. In nature they are more or less benign. 

We have grouped in the following pages those tumors now believed 
to be sarcomatous alterations of the covering and lining of blood- and 
lymph-vessels. These tissues are derived from the mesoderm, as is the 
case with tissues giving rise to sarcomata, and resemble these tumors 
in their manner of growth. The individual cells approach, however, 
the epithelial or carcinoma type. 



PROGRESSIVE TISSUE CHANGES 



203 



ENDOTHELIOMA 

This tumor, which is also sometimes designated endothelial cancer, 
resembles cancer very closely in histological appearances in some cases. 
It affects the pleura, peritoneum, and membranes of the brain most 
frequently, but may be found in the skin, walls of the blood-vessels, 
periosteum, bone-marrow, lymphatic glands, gums, ovary, testicle, 
liver, and salivary glands. The serous membranes when affected 
become greatly thickened, tough, and white in color (Fig. 71), and 
irregular elevations or nodules may occur. Metastasis is infrequent, 
but the adjacent organs are sometimes involved, and occasionally more 




Fig. 71. — Endothelioma of pleura: the pleural cavity was distended with effusion and the 
lung was compressed and invaded by secondary nodules. 

distant structures. Endotheliomata of the dura mater spring from 
the inner surface of that membrane and have a flattened nodular char- 
acter. Histologically they may present the concentric whorls of cells 
and calcification characteristic of psaynmomata. 

Histologically endothelioma is characterized by more or less tubular 
or acinus-like aggregations of endothelial cells. The latter vary in 
character from those which are distinctly endothelial to the most differ- 
entiated, which may be almost typical cylindrical epithelium (Fig. 72). 
Between these cellular columns or acini the connective tissue of the part 
affected may be seen in a normal state, though it is more frequently 
thickened by proliferation, and may grow into and around cell groups 



204 



A TEXT-BOOK OF PATHOLOGY 



to such an extent that they seem admixed or that the tumor cells de- 
generate. In the endotheliomata of serous membranes inspection of the 
sections shows that the columns of epithelioid cells occupy lymph-chan- 
nels, and it may be possible to demonstrate that the endothelium of 
the latter has been the starting-point of the cellular proliferation. In 
cases of carcinoma with penetration into the lymphatic channels it is 
notable, on the other hand, that the endothelial lining of the channels 
is uninvolved. Endotheliomata may in rare cases originate in the endo- 




Fig. 72. — Microscopical section from the case shown in Fig. 71. 

thelium of capillary blood-vessels. In these growths anastomotic chan- 
nels lined with endothelial cells or anastomozing columns of endothe- 
lial cells proclaim the origin from vessels. 

Psammoma 

This represents no distinct species of tumor growth, but rather a 
peculiarity of different kinds. The name refers to the presence of cal- 
careous matter like that of the brain-sand (acervulus cerebri) , and psam- 
moma has sometimes been called acervaloma. The calcareous matter 
occurs in the form of rounded masses or concentrically arranged whorls. 
The tumor elements themselves may be fibromatous, gliomatous, 
sarcomatous, endotheliomatous, or even adenomatous or carcinoma- 
tous. In most instances it is endotheliomata that present these 
appearances. Psammomata are met with in the membranes of the 
brain, the choroid plexus, and the pineal gland. 

Tumors from Nerve Tissues 

The various elements of adult nervous tissue are the descendents 
of the ectodermic cells lining the neural canal of the embryo. The 
tumors arising in nerve tissues contain the different elements in vary- 
ing grade of differentiation, and the tumors are usually named from the 



PROGRESSIVE TISSUE CHANGES 



205 



state of development. Naturally, the gangliomata and those containing 
chromaffin cells are of a higher grade than the tumors composed of 
abnormally proliferating simple nerve-cells, a very rare occurrence, or 
of glia. The ganglionar growths and those of some structures like 
the adrenal medulla, whose genesis is closely associated with the ner- 
vous system, frequently contain cells whose protoplasm stains granular 
brown when fixed with chrome salts {chromaffin cells). 

The glioma when pure is a well differentiated tumor, and is of 
sufficiently frequent occurrence and clinical importance to warrant 
separate treatment. Glia tissue plays an important part in most 
neuroblastomata. 

GLIOMA 

Definition. — The term "glioma" is applied to tumors composed 
of neuroglia with incompletely differentiated cells and many glia fibrils. 
It is difficult to draw a sharp line between the circumscribed tumors 
of this structure and the diffuse neurogliar hyperplasia or gliomatosis 
met with in certain cases. (See section on Diseases of the Nervous 
System.) 

Etiology. — It is probable that congenital defects of development 
play some part in the causation of these tumors, particularly in the forms 
more frequently spoken of as gliosis. 

Appearance. — A typical glioma is usually a solitary tumor, rounded 
in outline, though its limits are difficult to determine, as it merges 
gradually into the surrounding nervous tissue. Gliomata are some- 
what harder than the normal brain substance, and often the color is a 
little different, either more grayish or pink or reddish. Sometimes they 
are quite vascular and dark red. The 
normal shape of the part may be little 
disturbed, or there may be indefinite 
elevation. In size the tumor varies up 
to masses as large as a lemon. Diffuse 
gliomatosis causes a swelling of the af- 
fected parts, sometimes quite regular, 
at other times irregular. When the 
spinal cord is affected its thickness may Fig 73 ._ Glioma of the corpora 
be considerably increased. On section, quadrigemina (Perls), 

the area of gliomatosis is rather firm 

and grayish in color. Nearly always there is a tendency to excavation 
or cyst formation. In the cord this leads to the development of con- 
siderable cavities, as a rule communicating with the central canal. 

Seats. — Gliomata occur in the brain and less frequently in the spinal 
cord. In rare cases the cranial nerves have been involved (Fig. 73). In 
one case a glioma was found over the coccyx and sacrum, originating 
from the remains of the lower end of the neural canal. Glioma of the 
eyeball will be referred to below. Diffuse gliomatosis is particularly 
common in the cord. It is usually met with in the vicinity of the cavi- 
ties of the brain or cord. 




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A TEXT-BOOK OF PATHOLOGY 



Structure. — The minute structure of glioma varies consider- 
ably according to the type of neuroglia represented. In the typical 
glioma the cells contain rounded or oval nuclei, and the protoplasm is 
scanty. Polynuclear cells may occur among the glia elements. The 
glia cells possess great numbers of exceedingly fine fibrils attached and 
separate from the interstitial fibrils. Wavy intercellular fibrils (neurog- 
lia fibrils) lying parallel to the axis of the cells to which they belong are 
characteristic structures. They are not prolongations of the cells, but 
merely touch the cells at their sides, the extremities of the fibrils being 
free. These fibrils are distinguishable from the finer fibroglia fibrils 
of connective-tissue growths. The abundance of the fibrils varies in 
different gliomata, but is generally a rather marked feature. The more 
rapid the growth, the fewer the fibrils. These give the section a granular 
appearance when seen under low magnification. In other cases the 
cells are of the ependymal type, and occasionally they may be arranged 
around the blood-vessels in rosette-forms. These formations, however, 
constitute only a small part of the structure, the bulk being composed 
of round glia-cells. The number of cells and the density of the intercellu- 
lar network vary greatly. As a rule, the cells are larger than the normal 
neuroglia cells, and sometimes they contain several nuclei. The tumor 
is generally quite vascular, and occasionally telangiectatic vessels may 
be observed. Secondary hemorrhages are prone to occur in the latter 
case. Softening may occur, and occasionally sarcomatous transforma- 
tion has been described, though with doubtful propriety. Embryologic- 
ally the glia is an epithelial structure, and gliomata should, therefore, be 
classified as epithelial tumors, and sarcomatous transformation is im- 
probable. 

Diffuse gliomatosis has similar microscopical appearances, though 
the tissue is likely to be more compact and less vascular. In the 
spinal cord the process begins as a subepithelial proliferation of the glia 
at the posterior raphe of the central canal, the lining epithelium of this, 
at the same time, undergoing a certain amount of proliferation. Sub- 
sequently the gliomatosis increases and cavities form within. These 
may be lined with epithelial or epithelioid cells which are occasionally 
ciliated. Gliomatosis in the brain or cord may also present itself in the 
form of scattered nodular hyperplasias of the neuroglia. 

Nature. — Glioma is essentially benign. It is dangerous mainly 
on account of the pressure it exerts. Active proliferation and eccentric 
growth may occasion a considerable local malignancy in some cases. 
It is these that were formerly described as cases of sarcomatous trans- 
formation. The growth of the tumor is rather slow. They do not 
seem to give metastasis outside of the nervous system. 

Glioma of the Retina. — This tumor is a primary one of the retina, but 
may later extend to the eyeball and along the optic nerve. It is com- 
posed of round cells with large nuclei, often arranged around blood- 
vessels in a way suggesting the structure of angiosarcoma. This appear- 
ance is due to the fact that the cells surrounding the blood-vessels are 
preserved, while those at a distance are degenerated. In addition to the 



PROGRESSIVE TISSUE CHANGES 



207 



round cells, there are often found cells resembling epithelium in their 
appearance and their arrangement, the latter being that of epithelial 
rosettes. Ganglional cells have occasionally been discovered. The cells re- 
sembling epithelium have been regarded as derivatives of the outer layers 
of the retina, and the term neuro-epithclioma has, therefore, been applied 
by some authors. Others regard it as a glioma in the strict sense of the 
word. In either case the origin of the tumor is undoubtedly ectodermic, 
and the growth must be classified among the epithelial tumors. It 
occurs most frequently in children, particularly in early life (two to 
four years), and often on both sides simultaneously. Family predis- 
position, in some cases, is very striking. Extension along the optic 
nerve or externally, and a tendency to recurrence after removal, indicate 
the malignant character of the growth. 

Glioma Ganglionare 

Definition. — This term indicates a form of mixed tumor composed 
of neuroglia and nerve-fibers with large ganglionar nerve-cells; also 
called neuroma ganglionare. 




Fig. 74. — Ganglio-glioma of corpus callosum. Note the large irregular, imperfect ganglion 
cells, the deeply staining round glia nuclei with large wavy hypertrophic fibrils. 

Etiology. — Probably congenital abnormality of development fur- 
nishes the groundwork for the subsequent development of these tumors. 



208 



A TEXT-BOOK OF PATHOLOGY 



Appearance. — A ganglionar glioma may resemble the ordinary 
glioma, occurring as a solitary tumor, the outlines of which are difficult to 
distinguish from the surrounding tissue. More frequently it occurs in 
the form of multiple nodular condensations scattered through the brain 
or cord. The contour of the affected parts may not be altered, and on 
section the growths may be recognized only by the light-colored patches 
and areas of increased density. A few cases of ganglionar gliomata of 
the spinal or sympathetic ganglia have been described. In these cases 
the tumors appear as rounded enlargements of the affected ganglia. 
Occasionally the nerve-roots are seats of these tumors; the suprarenal 
capsules may also be affected. 

Structure. — The definition indicates the usual structure. The glia 
fibrils are generally conspicuous in number, the nuclei being compara- 
tively few. Traversing the tumor there may be more or less abundant 
nerve-fibers with or without medullary sheaths. Large ganglionar cells 
may be found in considerable abundance or in small number. The 
vascularity of the growths differs greatly. 

Nature. — The nature of these tumors is the same as that of the ordi- 
nary glioma. 

NEUROMA 

Definition. — Strictly speaking, neuroma is the term applied to 
tumors composed of nerve-cells and nerve-fibers. Ordinarily, however, 
the name is given to fibrous growths springing from the perineurium or 
endoneurium of nerves. The terms true and false neuroma distinguish 
between the two forms. True neuromata are rare, but Wright has 
called attention to the true neurocytoma or neuroblastoma made of cells 
like those of sympathetic ganglia associated with delicate fibrils. The 
last do not stain like neuroglia tissue. The cells are small, with round, 
deeply staining nuclei and relatively little protoplasm. They frequently 
assume a rosette- or acinus-like arrangement. 

Etiology. — Very little is known regarding the causation. Injury 
may play a part, as in the case of amputation neuromata. 

Appearance. — False neuromata occur as nodular thickenings 
along the course of nerves. They may be fusiform or elongated, may 
extend considerable distances along the nerves, and may form networks 
of ridges or elevations when the peripheral nerves are involved (plexiform 
neuroma). As a rule, they are multiple, and sometimes occur in exceed- 
ingly great numbers, scattered over the entire body or involving a single 
part of the body, as the nerves of the arm or leg. After amputations 
rounded thickenings may occur at the ends of the nerves and cause 
painful conditions of the stump. 

Seats. — The peripheral nerves are most frequently involved, but 
the nerves may be implicated near their roots, or the terminal fibers 
within the organs may become affected. 

Structure. — Ordinary false neuroma consists of fibrous tissue 
in the form of reticular connective tissue with greater or less abun- 
dance of cells pushing aside or surrounding the nerve-fibers proper. 



PROGRESSIVE TISSUE CHANGES 



209 



The latter are prone to degenerate in consequence of the pressure. 
Proliferation of the nerve-fibers has sometimes been described, but it 
is doubtful whether such actually occurs. More probably the existing 
fibers increase in length and form a mass by curling at the end. 

True neuromata of two kinds are described: those composed of medul- 
lated, and those consisting of non-medullated, nerve-fibers. The former 
are called myelinic; the latter, amyelinic. " Neurosarcoma " is a modified 
neuroma in which atypical unrestrained proliferation occurs with a 
markedly inconspicuous interstitial tissue. In some the proliferated cells 
are of the epithelioid type. These tumors may occur in the cord. Occa- 
sionally a suggestion is given of acinus-like arrangement, and to this has 
been given the name "neuro-epithelioma." 

Nature. — Neuromata are painful tumors, but benign in a patho- 
logical sense. Their growth up to a certain point is often rapid. 

LEIOMYOMA 

Definition. — Leiomyoma, or myoma lsevieellulare, is a tumor 
growing from smooth muscle-fibers. Nearly always there is a cer- 
tain amount of fibrous tissue associated, and in the most common 
form, myomata of the uterus, there is always considerable fibrous 
tissue, and the term "fibromyoma" is appropriate. Occasionally a few 
unstriped muscle cells may be seen in tumors of other kinds. 

Etiology. — Some of the myomata of the uterus exhibit glandular 
acini in the interior, which suggest their origin from congenitally mis- 
placed portions of the Wolffian body or duct of Muller. These misplaced 
structures are assumed to cause an irritation of the surrounding muscle 
cells. This, however, is by no means certain. In other cases there are 
features suggesting that irritation is the important cause, though this 
also remains to be proved. 

Appearance. — Leiomyomata are usually rounded growths, vary- 
ing in size from minute nodules to huge solid masses weighing as 
much as 60 to 70 pounds. The largest (heaviest) solid tumor ever 
seen by us was a degenerated fibromyoma weighing 80 pounds. Leio- 
myomata are surrounded by a capsule more or less well developed 
and are generally quite hard, though secondary degeneration at times 
alters the consistency, making the tumor quite soft in the case of mucoid 
transformation, or stony hard when calcification has occurred. On 
section through the growths the stratified or fasciculated arrangement 
of the cells is visible to the naked eye. Concentric layers may be ap- 
parent, or a more wavy irregularity may be seen. They are grayish 
or flesh colored, or in rare instances quite red (myoma cavernosum), in 
consequence of enlarged vascular channels. Central softening may lead 
to cystic change (myoma cysticum). 

When the myomata spring from the submucous or subserous tissues 
they may become polypoid, hanging from a point of attachment by a 
narrow pedicle. In rare instances the latter is severed and the tumor 
becomes a free body. Submucous myomata of the uterus may thus 

14 



210 



A TEXT-BOOK OF PATHOLOGY 



eventually be discharged after a spurious labor. Subserous myomata 
may become free in the peritoneal cavity. 

Gross myomata of the uterus may have three situations — submucous, 
subserous, or interstitial. Originally, all true forms begin as interstitial. 
In the latter the tumor occupies the wall of the uterus without any 
particular projection on either surface. Uterine myomata are usually 
multiple, occur during the third and fourth decades of life, continuing 
their growth until the menopause, and usually decreasing after that 
epoch. They endanger life by their pressure and by the copious 
uterine hemorrhages which they occasion. Very frequently salpingitis 
is associated, and recently attention has been called to degenerated 
conditions of the myocardium in patients suffering from uterine 
fibroids. 

Myomata of the skin occur in younger patients, even in childhood, 
and are generally multiple and often painful (tubercula dolorosa). 

Seats. — The common situations are the uterus, the gastro-intestinal 
tract, and the ovaries; the less common seats are the walls of the blood- 



Structure. — Microscopically, the tumor presents a characteristic ap- 
pearance. Bundles of muscle cells are seen running in different directions. 
Those cut longitudinally show cylindrical nuclei as the most conspicuous 
feature, the outlines of the cell being indistinct (Fig. 75). The proto- 
plasm stains well with eosin. Lying between the muscle cells are colla- 
gen and so-called myoglia fibrils, the latter being coarse lines lying along 
the sides of the cells, while the former are more delicate and are associ- 
ated with fibrous tissue cells. The picture of a leiomyoma is often sug- 
gestive of sarcoma, but may be distinguished by the greater regularity 
in direction of the cells in different bundles and by the more distinctly 
cylindrical outline of the nucleus. The cells of leiomyomata may be 
isolated by maceration of the sections in 20 per cent, solution of nitric 
acid for twenty minutes, or in 30 per cent, solution of caustic potash 
for fifteen minutes. They are spindle-shaped structures containing a 
nucleus about one-third the length of the entire cell. On section they 




Fig. 75. — Leiomyoma. 



vessels, the skin, and the nipple. 
In all situations the tumor springs 
from pre-existing unstriped mus- 
cle-fiber. In most cases, accord- 
ing to some authors, the origin is 
in the walls of the minute blood- 
vessels, but direct origin from the 
muscular layer of the affected 
organs, or from the erectores pilo- 
rum in the case of the skin, cannot 
be denied. Myomatous meta- 
plasia of the connective tissue, as 
in the case of myomata originat- 
ing in the areas of old pleural 
thickening, has been assumed, but 
is improbable. 



PROGRESSIVE TISSUE CHANGES 



211 



can be differentiated from fibrous tissue cells by showing an appreciable 
amount of protoplasm around a rod-shaped nucleus, while the connect- 
ive-tissue cell has very little protoplasm about a short spindle-shaped 
nucleus. Considerable elastic tissue is found in some leiomyomata, es- 
pecially in the younger areas. 

Leiomyomata are generally poor in blood-vessels, but may show a 
telangiectatic condition of the vessels. The lymphatic channels may 
similarly dilate, forming cystic spaces containing spontaneously coagu- 
lable material. 

Of the degenerative changes, calcification is the most common, par- 
ticularly in the uterine fibromyomata. This begins in the center of the 
tumor, but may eventually involve the whole mass. Myxomatous 
change may occur in myomata containing much fibrous tissue, and sarco- 
matous transformation has been described, but is rare. 

The sarcomatous change has been explained by some as a metaplasia 
of the muscle cells, by others as arising from fibroblasts. The latter is 
probably correct. Many so-called sarcomata coming from smooth 
muscle tumors are doubtless merely actively proliferating, therefore 
softening, leiomyomata. 

Uterine myomata do not all present the same appearance. Some are 
all of muscular nature, some are wholly fibrous, and we have all possible 
intermediate grades. Those in which fibrous tissue preponderates may 
be called "fibroids." Young tumors are mostly muscular; old ones, 
mostly fibrous. Whether this is purely a metaplasia or an overgrowth 
of the muscle by fibrous supporting tissue is not settled. The origin 
of the myomatous tissue is said by some not to be the uterine muscle 
bundles, but the muscularis of blood-vessels. The vessels of myomata 
have very wide walls with wide muscular coats. 

Adenomyoma of the uterus is a myoma with structures like gland 
acini. These are variously explained as coming from remains of the 
Wolffian body or Midler's duct, from the mucous glands, or inversions 
of the serous covering. They may undergo carcinomatous increase, but 
adenomyomata are not malignant per se. 

Nature. — The nature is eminently benign. Myomata of the 
digestive tract may cause occlusion or strangulation, or by their weight 
may exercise serious traction. Uterine myomata are dangerous in the 
ways already indicated. The growth is usually slow. 



RHABDOMYOMA 

Definition. — Rhabdomyoma, or myoma striocellulare, is a tumor 
containing more or less striped muscle-fiber. Usually there is but a 
small quantity of the latter, the bulk of the tumor being of some other 
tissue, most frequently sarcomatous. 

Etiology. — Congenital defective development seems an important 
cause, as the tumors occur in early life and in situations in which striped 
muscle-fiber does not normally occur. 



212 



A TEXT-BOOK OF PATHOLOGY 



Appearance and Seats. — The rhabdomyomata of the kidney 
(the most frequent seat) present themselves as large rounded or irregular 
masses, more or less encapsulated. In the testicle they are similar, 
though of smaller size. A few cases have been described in which irregu- 
lar tumors of the retroperitoneal tissues have contained muscle-fibers. 

Structure. — The microscopical appearance is usually that of a 
spindle-celled sarcoma, containing more or less striped muscle-fibers. 
These are elongated spindle-shaped cells, partly striated, and suggesting 
embryonal muscle-tissue and rarely more fully developed muscle-fibers. 
Large areas of the tumor may contain no muscle-fiber at all, while 
certain portions are richly supplied. Adenomatous elements are not 
rarely associated. The tumors of the kidney which contain striped 
muscle-fibers are, in the main, sarcomatous or adenosarcomatous. 

Nature. — These tumors are malignant in proportion as the sar- 
comatous element is predominant. This sarcomatous nature is indi- 
cated by activity of proliferation, spread, and metastasis. Metastasis 
is, however, infrequent. General cachexia and hemorrhages reduce 
the vitality and lead to fatal termination. 

Epithelial Tumors 

This heading covers all the tumors in which the cellular unit is the 
epithelial cell of covering or glandular tissues, supported by more or less 
connective tissue, the relations of the two determining the character of 
the growth. In some arrangements there is simply an exaggeration of 
the normal, the so-called typical epithelial growths, while in others there 
is wholly new or atypical arrangement of the elements. The first, like 
papilloma, are essential benign, while the second group is best exempli- 
fied by the malignant carcinoma. 

PAPILLOMA 

Definition. — The term "papilloma" indicates a tumor arising from 
a surface and covered with epithelium somewhat as the epidermis caps 
the papillae of the corium. 

Etiology. — It is difficult to draw a line between certain papillo- 
matous growths that are the result of chronic irritation and others that 
arise in a seemingly spontaneous manner. It would appear that irri- 
tation is an important factor in most, if not all, cases, but there is also, 
no doubt, some form of predisposition. Whether this resides in structural 
peculiarities or not is difficult to determine. A peculiar form of inflam- 
matory growth resembling the spontaneous papillomata is that known as 
venereal wart. It occurs about the genitalia or anus and especially after 
gonorrhea. Another form of inflammatory papillomata is that found in 
the mucous membranes surrounding carcinomata or chronic ulcerations 
of syphilitic or other kinds (Fig. 76). 

Appearance. — The most familiar form of papilloma is that which 
occurs in the skin and which is commonly called wart. Warts or pap- 



PROGRESSIVE TISSUE CHANGES 



213 



illomata may be single, but more frequently occur in groups, and there 
may be many growths in widely scattered areas of the body. A wart 
may be simply a smooth hemispherical elevation, or it may have a cauli- 
flower appearance. The epidermis covering it is, as a rule, somewhat 
more granular or rough than that of the normal skin. The size of 
these growths varies from minute points to nodules as large as a walnut. 
On the mucous surfaces, especially where the epithelial covering is colum- 
nar, the papilloma presents itself as a soft and more distinctly cauliflower 
growth (Fig. 77). It is red in color, or, if the epithelium is stratified and 
squamous, grayish or pink. The growth is usually comparatively hard 
when covered by squamous epithelium. 




Fig. 76. — Various grades of warts and cutaneous papillomata (Perls). 

Two varieties are sometimes distinguished: the hard papillomata, 
such as those which occur in the skin; and the soft papillomata, or the 
form usually seen in the mucous membranes. 

Seats. — Papillomata occur in the skin of the neck, hands, back, 
and other parts, and in the mucous membranes, particularly in the 
bladder, larynx, nasal chambers, and gastro-intestinal tract. Small 
papillomatous outgrowths may spring from the lining membrane of 
glandular ducts, as in the breast or ovary. These may lead to subse- 
quent cystic change in the organ, or they may arise after cystic change 
has begun by proliferation of the lining membrane of the cyst. In a simi- 
lar manner papillomatous elevations may occur within the cavities of 
cystic adenomata (see below). 



214 



A. TEXT-BOOK OF PATHOLOGY 



Structure. — The essential parts of papilloma are the center or 
groundwork of connective tissue containing blood-vessels and the epi- 
thelial covering. In the skin the growth 
imitates the normal papillae, all portions 
of the latter, however, being greatly ex- 
aggerated, and the papilla with its cover- 
ing of epidermis being raised above the 
surface instead of having its usual seat 
below the surface with the epidermal 
covering level with the surrounding parts. 
When there is tendency tb cauliflower ap- 
pearance the papilloma shows a branch- 
ing form on vertical section. Each of 
the branches contains a connective-tissue 
framework with an epithelial covering. 
The latter consists of stratified, squamous 
cells and shows a decided tendency to horny 
change. Distinct concentric whorls of 
horny epithelium, such as occur frequently 
in epitheliomata of the skin, may be met 
with in papillomata. In some cases the 
amount of connective-tissue groundwork in 
the papilloma is excessive; in others the 
new growth consists almost entirely of pro- 
liferated epithelium. In some of these 
latter cases the resemblance to epithelioma 
may be quite suggestive, but a distinction can be made by observing 
that the tumor tends to grow outward rather than into the deeper 




Fig. 77. — Papillomata of the 
vocal cords (from a specimen in 
the Museum of the Philadelphia 
Hospital) . 




structures, and always shows some connective-tissue stroma at least. 
The papillomata of the mucous membranes differ according to their 



PROGRESSIVE TISSUE CHANGES 



215 



situation. In the larynx and other portions covered with squamous 
epithelium they may present much the same appearance as that seen 
in the skin, though the epithelium, as a rule, remains softer. There 
are cases, however, in which a distinct pachydermatous change is found 
in the epithelial covering of 
papillomata. lathe gastro- 
intestinal tract and in the 
bladder papillomata are 
prone to be soft and villous 
in appearance and are cov- 
ered with a scantier epithe- 
lial coating. Cystic change 
is not unusual as a result 
of degenerative processes or 
of distention of the mucous 
glands. Occasionally hem- 
orrhage occurs from papil- 
loma, particularly of the 
villous variety. Melanotic 
pigment is sometimes found 
in warts. 

Nature. — The nature of 

these tumors is benign, but Fig. 79.— Papilloma of the scalp. The branching 

thev mar be destructive of fibr 9 u ? stroma is . c ° v f. red by an abnormally thick- 

1 * , . ened, irregular epithelium (Boyce). 

the general health in con- 
sequence of repeated hemorrhages or by interfering with the function of 
the organ or part in which they are situated. In some cases they are 
supposed to become malignant, but this has not been definitely proved. 

ADENOMA 

Definition. — This is the term applied to a new growth corre- 
sponding more or less in structure with compound epithelial glands, and, 
therefore, presenting acini or tubules containing glandular epithelial 
cells (cylindrical or polyhedral) growing upon a basement-membrane, 
and a reticulum of connective tissue and blood-vessels. It is difficult 
to separate from true adenoma simple glandular hyperplasia on the 
one hand and carcinoma on the other. This will be discussed in re- 
ferring to the structure. 

Etiology. — The causation of adenoma is obscure. In some cases 
congenital misplacements of tissue-elements appear to play a part, 
as is seen in the cases of adenomata of the kidney having the structure 
of suprarenal bodies. These tumors which, it is true, some authorities 
refuse to consider as adenomata, have a general resemblance to adeno- 
mata and spring from remnants of suprarenal tissues embedded in 
the kidney substance. Traumatism may be a factor in the etiology 
by exciting the proliferation of such misplaced tissue elements. In 
other cases the ordinary glandular structures seem to be stimulated to 




216 



A TEXT-BOOK OF PATHOLOGY 



abnormal hyperplasia and tumor growth in consequence of continued 
irritation. Instances of this sort are frequently seen in the gastro- 
intestinal mucous membranes, notably in the stomach and lower part 
of the colon, in certain cases of chronic gastritis and old dysenteries. 

Appearance. — The appearances of adenomata vary greatly with 
their seat. On the mucous surfaces there may be a simple thickening 
or more or less diffuse and irregular elevation of the surface, or in other 
cases distinct papillomatous outgrowths and rarely definite nodular 
tumors. In some of these cases the condition is purely one of inflamma- 
tory hyperplasia; in other cases there is undoubted tumor growth. No 
sharp demarcation can be established. In the substance of the organs 
adenomata occur as nodular tumors, usually singly and well circum- 
scribed, and not rarely surrounded by a fibrous capsule. They are 
moderately firm, and on section whitish or pink in color. Sometimes 
cystic change occurs as the result of dilatation of the glandular acini or 
in consequence of degenerative softening; in these cases the consistence 
is correspondingly altered. 

Seats. — Among the situations in which adenoma is frequent may 
be mentioned the mucous membranes, the skin, and certain organs, 
notably the mammary gland, liver, kidney, suprarenal bodies, thyroid 
gland, and ovaries. Clinically important seats are the pylorus, the duod- 
enal papilla, the rectum, and the uterus. In these situations adenomata 
spring from the epithelial tubules or mucous glands. In the skin the 
points of origin are the sebaceous and sweat-glands. 

Structure. — The definition in general indicates the structure 
of these tumors. They are more or less typical; that is to say, there 
are acini of normal appearance presenting a single layer of columnar 
epithelium, with perhaps in places a tendency to heaping up the several 
rows of epithelial cells. In the simple adenomata there is usually one 
layer. The greater the number of layers of epithelial cells, the greater 
the tendency to malignant growth; such a condition is found in adenoma 
malignum along with other features. The acini are well inclosed by 
a surrounding connective-tissue reticulum, and the appearance of normal 
gland tissue is thus produced. Unlike normal glands, there are no 
excretory ducts, or, at most, imperfectly developed ducts. 

Two varieties of adenoma are sometimes distinguished: the tubular 
and the racemose or alveolar. In the former the glandular system is 
simple and consists of tubular formations lined with columnar epithelial 
cells; in the latter the appearance is that of more complicated glands 
with closely aggregated acini of circular outline containing columnar 
and often cubical or polyhedral cells. The number of varieties may be 
carried further, however, for in the liver the adenomata resemble the 
normal liver structure rather than the ordinary glandular formation 
above described. In the suprarenal capsules and kidney the appear- 
ance is that of slightly atypical suprarenal structure, or in other cases 
that of embryonal renal tubules distended to form considerable cystic 
spaces, with partitions and inwardly projecting papillomatous elevations. 

With the further growth of adenomata the appearance may be little 



PROGRESSIVE TISSUE CHANGES 



217 



changed. In some cases considerable variations occur, and there is a 
tendency, more marked in some situations than in others, to active pro- 
liferation of the epithelium, which may cause a considerable alteration 
in the histology of the tumor, and eventually transformation into definite 
carcinoma. The terms "adenocarcinoma," "destructive adenoma," and 
"malignant adenoma" are sometimes applied in such cases. The same 
names, however, are given to a type of adenoma characterized by the 
formation of abundant anastomosing or separated tubules and acini 
with comparatively little reticular tissue, and by the tendency to repe- 
tition of the same structure in the local extensions from the original 
growth and even in metastases (Fig. 80). 




Fig. 80. — Destructive adenoma (Beyea). 



The connective-tissue stroma of adenomata may be moderate 
in quantity or may be considerable. In some adenomatous prolifera- 
tions of the mucous membranes the number of gland acini or tubules 
may be relatively small, while the interglandular connective tissue 
shows active round-cell infiltration to a very considerable degree. 
Sometimes the interglandular tissue is distinctly sarcomatous (adeno- 
sarcoma). In other instances the bulk of the tumor may consist of 
connective tissue of fibrous character in which are embedded a rela- 
tively small number of glandular alveoli. In all of these cases it is 
difficult to determine whether the connective-tissue process was pri- 
mary and the epithelial secondary, or the reverse. 

As has been suggested, it is well-nigh impossible to distinguish between 
some adenomata and some hyperplasias. This is particularly true of 
hyperplastic growth without fibrous tissue. This condition is, how- 
ever, apt to follow the general architecture of the gland in question 
and is not apt to be encapsulated. The adenomata have a tendency to 
show small, normal sized, and cystic acini in the same field. It is like- 



218 



A TEXT-BOOK OF PATHOLOGY 



wise a task to differentiate chronic inflammation and fibro-adenoma. 
In the former nearly all gland tissue is compressed and cysts are rare. 
When present they soon loose their epithelium. In fibro-adenoma epi- 
thelial reduplication is pronounced and the fibrous tissue increase is 
more diffusely distributed. 

Secondary changes are common, the adenomata of the stomach and 
uterus being particularly prone to change their character to that of 
carcinoma. In these cases there may be noted active proliferation 
of the epithelial cells, so that acini or alveoli become completely filled, 
or that the ends of tubular structures become blocked up. There is 
a tendency to extension of epithelial infiltration beyond the limits of 
the acini, cancerous outgrowths being the result. In other cases the 




Fig. 81. — Adenoma of the mammary gland, with cystic enlargement of acini and abundant 
interglandular hyperplasia of connective tissue. 

malignancy is manifested by the excessive epithelial proliferation in the 
form of new acini of irregular character (see Fig. 80). Eventually the 
tumor may become purely carcinomatous; in other cases, however, it 
continues to increase in size, always retaining its adenocarcinomatous 
appearance, but never becoming typically carcinomatous. 

Degenerative changes may be met with in adenomata as in other 
tumors. Hyaline transformation or production of hyaline or myxoma- 
tous tissue in the stroma may give the tumor an appearance justifying 
the term "cylindroma" or "cylindro-adenoma." Such cases are rare. 
Myxomatous and even calcareous change may sometimes be observed. 
The connective-tissue stroma may proliferate actively and assume sar- 
comatous appearance — adenosarcoma. Cystic change may result from 



PROGRESSIVE TISSUE CHANGES 219 

gradual dilatation of the glandular acini or from distention of normal 
ducts or alveoli of the gland in which the tumor occurs. In these cases 
the terms "cystic adenoma" or "cystadenoma" are applicable (Fig. 81). 

Nature. — Adenomata are benign tumors. In some cases, however, 
a pure adenoma may give rise to metastasis. Those of the liver, for 
example, not rarely cause secondary deposits in the spleen and less 
frequently elsewhere. The adenomata of the thyroid gland similarly 
cause metastasis, though their structure does not in any way suggest a 
malignant growth. Destructive adenomata or adenocarcinomata are 
malignant in proportion to the amount of carcinomatous transformation 
on the one hand, or of atypical glandular proliferation on the other. 

The effect of adenomata on the general health is variable. They 
do not contribute to the general metabolism as far as is known, though 
occasionally biliary pigmentation of the adenomata of the liver, and 
even of their metastases, and the secretion of milk-like fluid in mammary 
adenomata evidence the partial preservation of function by the cells. 
The general health may be unfavorably influenced by adenomata of 
the mucous surfaces in consequence of their interference with normal 
functions or in consequence of secondary ulceration and hemorrhage. 

CARCINOMA 

Definition. — The terms "carcinoma" or "cancer" may be applied to 
tumors in which epithelial proliferations in the form of solid blocks or 
columns, or in the form of atypical acini, separated by more or less con- 
nective tissue, present themselves, the epithelial proliferation showing 
a tendency to extend beyond normal anatomical limits. It is extremely 
difficult to construct a definition that will be universally applicable. 
Some have regarded the tendency of the epithelial proliferation to break 
through the normal limits, and extend beyond the confines of the epi- 
thelial structures from which it rises, as the important fundamental 
element of carcinoma. Others have held that there is a peculiar atypical 
character in the epithelial cells themselves, shown by irregular cell 
division, hyperchromatosis, and other features. The older authors 
believed that polymorphism and certain irregularities of cell contour 
suffice to distinguish carcinoma-cells from normal cells or those of other 
tumors; but this polymorphism is now recognized to be the result entirely 
of compression in the growth of the tumor, and to be, therefore, accidental. 
Some have believed that the term "carcinoma" should include all epi- 
thelial tumors giving rise to metastasis, but this necessarily restricts 
the term too greatly on the one hand, and, on the other, includes cer- 
tain tumors probably purely adenomatous. We prefer to regard as car- 
cinoma any epithelial growth atypically reproducing certain glandular or 
other structures and showing a manifest tendency to irregular extension. 

Etiology. — The causes and nature of carcinoma are still obscure. 
A number of theories have been offered. These have been referred to 
in the discussion of the etiology of tumors in general. A brief reconsid- 
eration may be useful in this place: 



220 



A TEXT-BOOK OF PATHOLOGY 



(a) Congenital Theory. — The theory of Cohnheim regarding the 
etiology of tumors in general is less applicable to cancer than to certain 
other growths. There are a few examples, however, which would seem 
to prove that misplaced epithelial cells undergo carcinomatous pro- 
liferation; for example, there are cases of apparently primary carcinoma 
springing from bones which would seem to require this explanation. 
It is not always certain, however, that such cases are actually primary. 
The rarity of carcinomata in early life would seem to negative the 
congenital theory, and, at all events, would show that other influences 
of importance are requisite. 

(6) Traumatic Theory. — Clinicians are inclined to give great weight 
to this. A single traumatism probably has little importance, though 
women frequently state that they recall distinct injuries from which 
carcinomata of the breast have seemed to originate. It must be recalled 
that such injuries are sustained by practically every woman, and the 
presence of carcinoma would readily be attributed to a preceding hurt. 
In cases of epitheliomata of the lip in pipe-smokers, in the carcinomata of 
the scrotum and limbs in chimney-sweeps and paraffin-workers, in the 
skin of tar workers, and in cases of uterine carcinomata following lacera- 
tion of the cervix, the effect of chronic irritation would seem to be im- 
portant. The frequent association of gall-stones with carcinoma of the 
gall-bladder has often been considered in the same light. 

(c) Infectious Theory. — The peculiar growth of cancer, its destruc- 
tiveness of the general health, and its metastasis readily suggest an 
infective origin. Bacteriologists sought to isolate micro-organisms 
without success; later investigators have turned their attention to low 
forms of animal life — protozoa. (For further discussion, see p. 161.) 
A few successful experiments have been made at implantation from 
man to animals, or from one animal to another; but as Hanau, one of 
the early experimenters in this work, himself states, these experiments 
do not prove infectiousness. The secondary growths in the second 
animal may be simply of the nature of metastasis, due to implantation 
of the cancer-cells, followed by their proliferation. 

A renewal of activity in the study of the etiology of cancer during 
recent years, and with all the advantages of modern methods, has thus 
far led to no positive result. Statistical evidence, the probable cases 
of accidental infection in surgeons and others, the more or less suggest- 
ive results of experimental inoculation, and the distribution of cancer — 
lend some probability to the infectious theory, but it must be confessed 
that the evidence is far from positive. 

Among vegetable organisms to which etiological significance has been 
attributed are the blastomycetes, which some investigators claim to 
have found in every cancerous growth examined, and the assumed 
importance of which is further based upon the results of experimental 
infections with cultures of the organisms. The invariable occurrence 
of blastomycetes has, however, been disproved, and the experimental 
lesions are not really analogous with carcinoma. Many inter- and 
intracellular cancer parasites have been described. There are within 



PROGRESSIVE TISSUE CHANGES 



221 



and between the cells certain unusual bodies with rather definite stain- 
ing reactions seeming to pass through a metamorphosis. These are 
now explained as the results of nuclear degeneration or discharge of 
its chromatin. Still other intracellular bodies in cancer are to be ex- 
plained as the remains of ingested masses, since the cancer-cell in its 
progression into the surrounding tissue consumes cell detritus. None 
of these bodies can be held as proved causes of cancer. 

(d) Tumor Dyscrasia. — This indefinite term is supposed to indicate 
that certain peculiarities of the liquids of the body occasion the tend- 
ency to cancerous growth. No proof of the existence of any definite 
dyscrasia has ever been furnished, though it is not unlikely that some 
form of disposition to this growth acts as the predisposing cause, even 
if traumatism, infection, or other factors are the immediate cause. 

Certain conditions are supposed to precede and favor some cancers. 
Paget's disease of the nipple may precede mammary cancer, as also 
gastric ulcer may pave the way for carcinoma of the stomach. Previous 
benign epithelial growths may become carcinomatous, as indicated by 
their penetrative and greater proliferative powers, but not necessarily 
by any alteration of the cells themselves. 

Age plays an important part in the formation of carcinoma, as this 
tumor is essentially one of advanced years. Among 275 cases collected 
by Lubarsch, 55.6 per cent, occurred between the ages of forty-five and 
sixty-five. There were a few instances in childhood and early life. Be- 
tween fourteen and nineteen there were 1 .46 per cent. ; between twenty 
and twenty-five, 1.8 per cent.; between twenty-six and twenty-nine, 
1.1 per cent. The frequency in later life was formerly ascribed to some 
alteration in the vitality of the epithelial cells, rendering them more 
liable to abnormal proliferation. The nature and cause of such altera- 
tion, however, remain obscure and theoretical, though there is certainly 
a greater tendency to cancer growth as age increases. 

Heredity was formerly regarded as of great importance. Certainly 
in some cases there seems to be hereditary transmission of the tendency 
to develop carcinoma. 

Appearance. — Carcinomata differ considerably in appearance in 
different parts of the body. Those of the surface present themselves 
as more or less nodular, flat elevations. In the skin the nodules may 
remain hard and rather smooth, or they may soften upon the surface, 
forming unsightly ulcerations. In the mucous membranes the growths 
are more frequently soft and polypoid or cauliflower excrescences (Fig. 
82). Ulceration may occur on the surface of such elevations, or from the 
first the tumor may be of ulcerative character, causing spreading ex- 
cavations limited by thickened projecting edges. Carcinomata of the 
glandular organs form more or less nodular tumors or irregular infiltra- 
tions. These vary greatly in consistency, some being almost stony hard, 
others soft in consequence of their preponderating cellular character or 
of secondary degenerations. On section, the tumor is found to be white 
or grayish in color, generally somewhat translucent and glistening; 
milky liquid may ooze from the surface. Capsule formation is rarely 



222 



A TEXT-BOOK OF PATHOLOGY 



seen, though in occasional instances the normal connective tissue of the 
organ is pressed outward by the growth of the tumor, and thus forms an 
imperfect capsule. The primary growth is generally solitary. Occa- 
sionally instances are observed in which two separate masses develop 

simultaneously and apparently 
independent of each other, as 
in the two breasts. More fre- 
quently apparent multiplicity 
is caused by the early appear- 
ance and rapid growth of met- 
astases. 

Secondary carcinomata are 
nodular in character and 
nearly always multiple. The 
larger are often distinctly en- 
capsulated. Central softening 
or contraction of connective 
tissue may give the surface of 
the nodule an umbilicated 
character (Fig. 83) . The num- 
ber varies greatly, from a few 
large or small nodules to in- 
numerable tubercle-like forms in general carcinomatosis. In some situa- 
tions, as in bones, secondary carcinoma has an infiltrating character. 

Seats. — The situations in which carcinomata occur are very numer- 
ous; they invariably arise from pre-existing epithelial structures. In 




Fig. 83. — Metastatic nodules of carcinoma on the surface of the liver (Hanot and Gilbert). 

the rare instances in which a presumably primary carcinoma has oc- 
curred in bone or other connective tissues the presumption is war- 
ranted that the tumor originated from remnants of epithelial tissue left 
by faulty development. Among the frequent places of origin the most 




Fig. 82. — Carcinoma of the duodenal papilla 
(modified from Kast and Rumpel). 



PROGRESSIVE TISSUE CHANGES 223 

important are the uterus, the skin, the gastrointestinal tract, particu- 
larly the esophagus, pylorus, and rectum, the mammary gland, the 
ovaries; less frequently the liver, kidney, thyroid gland, prostate, or 
testicle may be the starting-point. Secondary carcinomata curiously 
do not often affect parts in which the primary growth is frequent. Of 
the many seats of secondary carcinoma, the lymphatic glands, the 
liver, spleen, lungs, heart, and serous membranes are the most im- 
portant. Secondary carcinoma of the bones is specially frequent after 
carcinoma of the breast or the thyroid gland. 

Structure. — The histology of carcinoma varies greatly in different 
situations and in different forms. There are two distinct elements in- 
volved — viz., epithelial cells and a connective-tissue stroma. The 




Fig. 84. — Epithelioma of skin, showing concentric arrangement and degeneration of cells. 

epithelial cells are medium sized or large, and have a rather large and 
clear nucleus; the shape of the cell, however, differs widely. In epi- 
theliomata of the skin the cells are large and usually of a squamous 
variety. In carcinomata of mucous membranes they are more often 
cylindrical or columnar, and there is a tendency to the formation of cu- 
boid or polyhedral epithelium. The last-named forms are habitually 
present in the cancers of glandular organs. The mutual compression 
exercised may occasion a polymorphous character, and the older writers 
wrongly regarded this as a feature by which a carcinoma-cell could be 
recognized as such. Secondary changes may occasion wide variations 
in the appearance of the cells; thus, the epithelia of cancers of the skin 
tend to become arranged in concentric whorls and at the same time 
to become somewhat glistening from horny transformation (Fig. 84). 



224 



A TEXT-BOOK OF PATHOLOGY 



The nucleus may be clear and quite structureless, or may show a dis- 
tinct nucleolus and a definite chromatin network. Karyokinetic fig- 
ures may be quite abundant and are frequently atypical. Degenerative 
changes (dropsical infiltration, myxomatous change, fatty degeneration) 
may alter the nucleus as well as the body of the cell. 

The epithelial cells are usually grouped as cylindrical and branching 
or anastomosing columns, or as irregular tubular formations, the tubules 
being of varying lengths. The explanation of the structure of the col- 
umns or tubules is that they are formed by the extension of the masses 
of proliferated cancer-cells along the lymph-channels and spaces of the 
tissue. Very often the section shows all the tubules cut transversely, 
and thus the appearance of glandular acini is given. In some cases the 
tubules are short and acinus-like; as a rule, however, the appearance is 




Fig. 85. — Carcinoma of uterus. 

only due to the manner of section. The acini differ strikingly from those 
of adenoma in showing several or many layers of cells instead of one, 
and there is the further difference that cellular outgrowths may be seen 
at the periphery of the acini, the cells having broken through the 
retaining wall (basement-membrane) and proliferated outside to form 
new clumps (Fig. 85). On examination of the epithelia within the acini 
it is found that those of the peripheral layer frequently retain the 
columnar character seen in the normal alveoli of the gland from which 
the tumor springs. 

The connective-tissue stroma of carcinoma is more or less dense, 
but practically is always of fibrous character. It is arranged in such 
manner as to form hollowed spaces or columns in which the epithelial 
structures already described are embedded. The connective tissue 



PROGRESSIVE TISSUE CHANGES 



225 



carries the blood-vessels. The lymph-vessels probably connect directly 
with the cell-nests. In general, the more connective tissue in a cancer, 
the less its malignancy; while the more cells, the greater its tendency to 
metastasis and recurrence. Recently attention has been called to the 
fact that elastic tissue is formed in the stroma of the tumor in varying 
abundance. Frequently infiltrating leukocytes and plasma-cells or 
mast-cells are seen within the stroma. When the stroma begins to 
grow and show atypical proliferative tendencies we have what is called 
ca rcino ma sa rco m a todes . 

The above description applies to the ordinary carcinoma of glandu- 
lar organs. Some difference is observable in the cancers of the skin and 
other external surfaces. In these the structure is rather that of much 
enlarged papillae, the interpapillary epithelial plugs penetrating into the 
deeper tissues. The cells in their early stages are similar to those of the 
deeper layers of the skin, are larger and more translucent than those 
of glandular cancers. Subsequently the cells tend to become of the 
squamous type and undergo more or less horny change. Hollow alveoli 
and acini are unusual in cancers of the skin, though such structures may 
occur in some cases. 

Degenerative Changes. — Carcinomata are quite prone to degenera- 
tions. In nearly all cases in which the tumor has reached considerable 
size more or less fatty degeneration of the cells becomes apparent. 
Preceding this or associated with it may be cloudy swelling or dropsical 
infiltration of the cells, rendering the nuclear outline less distinct and 
sometimes causing vacuolations. Irregular and multiform nuclear de- 
generations are met with, and probably occasion some at least of the 
structures known as parasites of cancer. The epitheliomata of the skin 
are particularly prone to a horny transformation, this occurring first 
and most prominently in the concentric whorls already described. In 
the adenocarcinomata of the ovaries and other genital organs of women 
the degenerated epithelial cells frequently undergo calcareous infil- 
tration, and psammomata are thus formed. Colloid degeneration of 
the epithelial cells is a rare event, and the term "colloid cancer" is gener- 
ally a misnomer, the real degeneration in most of these being myxoma- 
tous, affecting the connective tissue principally, though the epithelial 
cells are to a certain extent involved. Complete degeneration by 
myxomatous or associated myxomatous and fatty change may de- 
stroy all of the characteristics of the original tumor. In some cases cystic 
transformation occurs in organs the seat of cancer, or in the cancer 
itself. This may be due to occlusion and subsequent dilatation of the 
ducts of the organ or of the acini in the tumor, the cystic spaces becom- 
ing filled with mucoid or gelatinous material. In some instances cystic 
carcinomata are secondary developments originating in cystic adeno- 
mata. Hyalin change and pigmentation are rare in cancer. 

Hemorrhage occurs by ulceration of a large vessel. Inflammatory 
processes are quite common. Cancers on free surfaces are prone to 
undergo ulceration in consequence of irritation and infection. Among 
the micro-organisms discovered in such instances the staphylococcus 

15 



226 



A TEXT-BOOK OF PATHOLOGY 



and streptococcus are conspicuous. A distinct erysipelatous inflamma- 
tion may occur in cancers as in other structures. Invasion of tubercle 
bacilli and the growth of miliary tubercles in carcinoma are rare events, 
though they sometimes occur. Associations of carcinoma and tubercu- 
losis or syphilis may in other cases result from the secondary growth of 
cancer in pre-existing gummatous or other syphilitic lesions or in lupus. 
Practically all carcinomata show some leukocytic infiltration. The 
amount of this, however, varies greatly. In the healthy tissue border- 
ing carcinomata there is always an inflammatory infiltration of round 
cells, but this does not limit the growth like a capsule. A carcinoma 
is probably never sharply marginated. 

Nature. — Carcinoma is essentially malignant, the degree of malig- 
nancy depending, however, upon the seat and upon certain peculiarities 
of the individual. Sometimes a small growth may remain practically 
latent for a long time, until accidental circumstances, like traumatism, 
intercurrent disease, pregnancy, or the like, stimulate active growth. 
Its rate of growth is variable, but chiefly it is progressive, regardless of 
speed. Occasionally there are remissions or even cessations, with retro- 
gression and absorption, but this latter is rare. 

Carcinoma exhibits all the elements of malignancy: the tendency to 
recur after removal, metastasis, and general deterioration of the health. 
Recurrence after removal is most readily explained upon the assumption 
that the entire growth has not been removed. Microscopical studies 
show that the area of infiltration is usually much greater than the naked- 
eye appearances would indicate, and this explains why the surgeon 
seldom removes the whole disease. Metastasis, as a rule, follows the 
lymphatic channels, and thus primarily involves the lymphatic glands 
in the neighborhood of the growth. The process may be explained 
as follows: Some of the epithelial cells in their advancing prolifera- 
tion penetrate the lymphatic channels and are carried in the lymph- 
stream to the nearest lymphatic gland, where they again proliferate and 
form secondary nodules; from these a similar extension occurs, and 
eventually widespread metastasis results. Less frequently the primary 
growth penetrates the walls of a vein and metastasis occurs through 
the circulation. This is quite common in the case of cancers of the 
stomach or intestines. The metastatic foci first spread through the 
portal circulation to the liver. In still other instances secondary 
growths result from mechanical transportation in the movements of the 
body; thus, in carcinomata of the abdominal organs the peristaltic move- 
ments may transfer particles to different parts of the abdominal cavity. 

Pathological Physiology. — The general health of patients suffering 
with carcinoma is affected very profoundly, though the manner in 
which this occurs remains obscure. It would seem to be of the nature 
of a toxemia. (See page 161.) Emaciation and loss of strength are 
habitual, though often, perhaps, in large part the result of interference 
with organic functions, as, for example, in carcinoma of the stomach. 
Progressive anemia may make its appearance, the red corpuscles becom- 
ing less abundant and the quantity of hemoglobin falling decidedly. 



PROGRESSIVE TISSUE CHANGES 227 

There is usually a moderate amount of leukocytosis, the large mononu- 
clear forms increasing particularly. Toward the end of life the tissue 
destruction increases greatly, though the excretory products of such 
may not be notably increased in the excretions in consequence of failing 
circulation and imperfect renal function. At this stage the accumula- 
tion of such products in the blood may lead to sudden death from coma. 
(See Acid-intoxication.) Hemorrhages and ulcerations may also con- 
tribute to the impairment of health in cases of cancer. 

Varieties of Carcinoma 

There are several forms of cancer sufficiently different to require 
separate description. The classification of these is generally based 
upon the character and arrangement of the epithelium. We may 
distinguish (1) epitheliomata, carcinomata composed of surface epithe- 
lium, either (a) squamous or (b) cylindrical, and (2) glandular carcino- 
mata, having either (a) more or less distinct adenomatous structure or 
(b) solid plugs or columns of epithelial cells, or (c) a mixture of acini 
and solid columns. 

Epithelioma 

This form, which consists of surface epithelium, is of two varieties, 
the squamous and the cylindrical. 

Squamous epithelioma occurs in the skin or mucous mem- 
branes, where squamous epithelium exists normally. Among the fre- 
quent seats are the lips, the esophagus, the larynx, and the cervix uteri. 
Occasionally squamous epithelioma arises in parts normally covered 
by other kinds of epithelium, as, for example, in the fundus of the uterus. 
In these instances there is probably a primary metaplasia of the epi- 
thelium followed by carcinomatous growth. Even in carcinomata of 
the breast some of the acini may present metaplasia of the cells to the 
squamous type. Squamous epitheliomata present themselves as nodu- 
lar, wart-like elevations of the skin or mucous membrane, tending to 
become ulcerated on the surface, with little tendency to hemorrhage. 
Those of the mucous surfaces are more elevated and softer. Grossly, on 
section, they appear as firm white or gray masses, with soft areas of cel- 
lular growth and shiny white strise of connective tissue. Histologically 
there are seen branching columns of epithelial cells extending downward 
into a stroma, well dotted with round cells from the papillse of the skin, 
into the deeper structures. These consist of large translucent squamous 
cells which show a tendency to arrange themselves in certain places 
concentrically to form epithelial perles, taking acid dyes well. The 
latter frequently undergo a horny transformation and sometimes even 
calcareous change (Fig. 86). The same structures occasionally occur in 
papillomata, but much less frequently. Metastasis is frequently seen 
in the neighboring lymphatic glands, but the malignancy is less marked 
than in glandular carcinomata. 

Some authors have described as a separate form skin cancers com- 



228 



A TEXT-BOOK OF PATHOLOGY 



posed of cuboid or polymorphous cells resembling those of the basal layer 
(Malpighian layer) of the skin and their embryonal equivalents. This 
is the so-called epithelioma or carcinoma basocellulare. Rodent ulcer 

belongs to this group, and while we 
do not agree that this is a different 
tumor, it varies from the typical in 
having greater cellular content of 
polymorphous cells and a paucity 
of pearls. As a matter of fact, all 
cancers of the skin originate from the 
basal cells, and the special variety 
alluded to differs from the ordinary 
type only in the fact that the cells 
do not become transformed, as in the 
normal growth of skin and in ordi- 
nary epitheliomata, into squamous 
cells. Such forms originate from the 
hair-follicles, sweat-glands and seba- 
ceous glands, as well as from the 
basal layer of the epiderm. 
Other varieties of epithelioma have been described depending upon 
the shape, arrangement, and alteration in the cell-nests. The cystic epi- 
thelioma is of the basal cell type, with degeneration of cell-nests and 




Fig. 87. — Cylindrical epithelioma of the intestine (Perls). 



the formation of cysts. All such forms are but accidental modifications 
and have no separate place in histogenesis. The name "epidermoid 
carcinoma" is given to those infiltrating growths which so retain the 




Fig. 86. — Squamous epithelioma, 
showing whorls of epithelial cells with 
central degeneration (from a photo- 
graph by Dr. W. M. Gray). 



PROGRESSIVE TISSUE CHANGES 



229 



stratification of the epidermal layers, or which assume this arrangement 
when not growing from epidermis. 

Cylindrical Epithelioma. — This form is composed of columnar 
or cylindrical epithelium. It is frequent in the mucous membranes, 
especially in the gastro-intestinal tract and the uterus. The epi- 
thelial cells of the tubular glands or sometimes those of the surfaces 
form the starting-point of the growth. More or less acinus-like tubular 
structures, composed of a layer of epithelial cells, or more frequently 
of a number of layers of epithelia, the outer layer being often distinctly 
columnar, constitute the characteristic feature of the tumor (Fig. 87). 
In the later stages the acini become filled with proliferated epithelial 
cells of various shapes and the cylindrical or tubular character of the 
lining is lost. Carcinomata of the kidney, liver, and mammary gland, 
though not originating from surface epithelium, strictly speaking, may 
be of the cylindrical form. Cylindrical epitheliomata more nearly re- 
semble the glandular carcinomata in their malignancy and general be- 
havior than the squamous variety. 




mBMSm 



Glandular Carcinoma 

This term includes the carcinomata that have a resemblance to 
racemose glands in their histological structure. They consist of acini or 
alveoli containing epithelial 



cells, visually in several layers 
or completely filling the lu- 
men, and a stroma of con- 
nective tissue. Some authors 
distinguish three forms: the 
simple, the medullary or en- 
cephaloid, and the scirrhoxis. 
These are simply variations 
of the same tumor. In the 
simple form there is a com- 
bination of epithelium and 
stroma in about the propor- 
tion seen in normal glands. 
The tumor is, therefore, 
neither strikingly hard nor 
soft. In the medullary or 
soft carcinoma the amount 
of epithelium is excessive and the tumor has a soft character (Fig. 88) ; 
while the scirrhous, or hard, cancer is an indurated form, due to excess 
of fibrous tissue and deficiency of the epithelium (Fig. 89). 

The glandular cancers are more or less nodular or infiltrating growths, 
varying in consistency in different cases, but having, on section, a glisten- 
ing white color with a certain amount of translucency. Milky liquid 
exudes from the surface on section. This is composed of albuminous 
fluid containing degenerated epithelium and free oil-droplets. Among 




. — Medullary carcinoma of breast. 



230 



A TEXT-BOOK OF PATHOLOGY 



the seats in which these forms occur the most important are the pylorus 
and other mucous surfaces, the mammary gland, the pancreas, kidneys, 
ovaries, and testicles. Widespread metastasis and other features of 




malignancy are noted. In the 
case of the scirrhous form the 
primary tumor may be strik- 
ingly small in comparison with 
the amount of metastatic de- 
posit. We may further divide 
glandular cancers according to 
the source from which they 
arise or as to the general archi- 
tecture they retain during the 
earlier stages. Thus we may 
speak of (1) columnar epithe- 
lial carcinoma when through- 
out the formative stages the 
long narrow cells are retained. 
These grow from tubular 
glands with cylindrical epithe- 



Fig. 89.-Scirrhous cancer of breast (Warren). lium like in the intestinal 

tract. (2) Duct cancer when 
cuboidal cells predominate and the general arrangement is tubular. 
(3) Acinous cancer when the acinus grouping, with more or less distinct 
cell-nests having a low or polymorphous epithelium, predominates. 



Special Forms of Cancer 

There are degenerations in some cancers which give them peculiar 
physical and chemical properties. Such alterations do not justify a 




Fig. 90. — Colloid cancer of the breast, showing myxomatous change in the stroma and 
fatty degeneration and partial disappearance of the epithelial cells (Perls). 

pathological separation, but clinically they have an importance. The 
most important are mucoid and colloid. In the former the interstitial 
tissue undergoes myxomatous change, making the tumor soft and dis- 



PROGRESSIVE TISSUE CHANGES 



231 



tended with a viscid material. In colloid cancer the cells undergo the 
change. 

The term "colloid" is usually a misnomer, as most of the colloid 
cancers contain no colloid material. The name gelatinous would be 
more appropriate, but has not been generally accepted. Such colloid can- 
cers are met with in the stomach and intestinal tract, in the mammary 
gland, and in the ovaries. The tumor has a peculiar transparent, glis- 
tening appearance. The entire 
mass may be uniformly jelly-like or 
only portions of it are affected. Mi- 
croscopically mucoid degeneration of 
the epithelial cells and stroma is dis- 
covered (Fig. 90). In some cases no 
trace of carcinomatous tissue may 
be discoverable, the whole tumor 
having undergone degeneration. De- 
generative cancers frequently spread 
by direct extension, and the entire 
abdominal cavity may become filled 
with material representing degener- 
ated secondary growths. Occasion- 
ally the same kind of peritoneal 
growths seem to originate primarily 
in the peritoneum; the origin of 
these may be fetal remnants of epi- 
thelial tissue (Fig. 91). 

True colloid cancer — that is, car- 
cinoma with colloid degeneration 
of the epithelium — is sometimes 
seen, though it is very rare. It oc- 
casionally causes a gross appearance resembling that of sarcomatous 
cylindroma, and the term carcinomatous cylindroma has been applied. 

CYSTS 

Definition. — This term includes pathological formations of varied 
character. Some are true tumors; others are of quite different nature. 

The term "cyst" is applied to pathological formations consisting of 
a more or less well-defined wall and enclosing liquid or semiliquid con- 
tents of different character from the surrounding parts. This definition 
is not entirely applicable, as certain structures that do not present a 
definite capsule are sometimes termed "cysts." Accordingly, we may dis- 
tinguish between true cysts and cyst-like formations or cystoids, the for- 
mer being enclosed by a capsule lined with epithelium or endothelium; 
the latter merely presenting a circumscribed collection of softened 
material. 

Classification. — According to the method of formation, we dis- 
tinguish retention cysts, softening cysts, cysts due to the presence of 




Fig. 91. — Colloid cancer of the peritoneum 
(modified from Birch-Hirschf eld) . 



232 



A TEXT-BOOK OF PATHOLOGY 



foreign bodies, and proliferation cysts. There are also cysts which 
owe their origin to some faulty development in utero. They are in a 
sense teratomatous and we shall consider them under a separate heading. 

Retention cysts are formed when the excretory ducts of a gland 
become occluded and the secretions accumulate and cause distention 
of the acini or of parts of the duct. Among such cysts may be named 
the distended sebaceous glands of the skin in the formations called 
wens; the cysts of the salivary or small mucous glands or ducts under 
the tongue, called ranulce; retention cysts formed in the uriniferous 
tubules, the tubules of the ovary, or in the parovarium, in the acini and 
ducts of the mammae, pancreas, and other glands. An entire organ 
may become converted into a cyst, as in cases of distention of the kidney 
(hydronephrosis) from obstruction of the ureter. 

These cysts are distinguished by the fact that they have a dis- 
tinct connective-tissue wall lined with epithelium or endothelium. 
The contents of the cyst depend upon the part in which the formation 
has taken place. 

Softening cysts occur in consequence of degenerative softening of 
normal or pathological tissues. They are not rarely the result of hemor- 
rhage, the blood-clot first becoming inspissated and then serous exuda- 
tion occurring in the area of hemorrhage. Softening cysts are very 
common in tumors of different kinds. 

Cysts due to foreign bodies are, in part, softening cysts. The tissues 
in the immediate vicinity may be injured and undergo necrotic soften- 
ing, while connective-tissue reaction produces a capsule. This form of 
cyst is most frequently the result of invasion of parasites, and the cyst 
contents may be composed of the parasite or the parasite and tissue 
elements more or less degenerated. 

Proliferation Cysts. — This term is applied to formations more 
closely analogous to true tumors than those mentioned before. They 
merit more extended description than the other forms of cysts, and may 
be designated as epithelial cysts. 

Epithelial Cysts 

Definition. — In certain glandular organs, notably the ovary and 
mammary gland, cystic formations occur which present striking appear- 
ances, and, though perhaps they represent adenomatous or carcinomatous 
new growths, are so striking as to deserve special mention. 

Etiology. — These growths, in part at least, result from obstruction 
of excretory ducts and subsequent irritation by retained secretions. 
Congenital abnormalities of structure may possibly play a part in their 
causation. 

Appearance. — Cystomata may be single or multiple, the entire 
tumor being composed either of a single cyst or of one large cyst sub- 
divided into many smaller ones; or, again, of numerous separate and un- 
connected cysts of varying size. On section, the cystic cavities are found 
to contain more or less serous or gelatinous liquid, and sometimes hemor- 



PROGRESSIVE TISSUE CHANGES 



233 



rhagic fluid is observed. Most frequently the liquid is gelatinous or 
ropy, and is commonly spoken of as colloid material. The inner lining 
of the cyst may be smooth, like a serous or mucous surface, or elevated 
irregularly in the form of polypoid outgrowths into the cavity of the 
cyst. The entire cyst may thus be filled with papillomatous elevations 
from the epithelial lining. The term papuliferous or proliferative cysto- 
mata is given to these forms (Fig. 92). The size of cystomata varies 
from minute tumors not larger than a pea to enormous masses weighing 
as much as 60 or 80 pounds. Secondary degenerations may occur 
in the form of softening, hemorrhage, or calcification. 

Seats. — The mammary gland and ovary are the principal situations 
in which tumors of this description are met with, but analogous growths 
may make their appearance in any of the glandular organs. 




Fig. 92. — Papuliferous adenocystoma of the kidney (Karg and Schmorl). 

Structure. — Microscopically, these growths present cystic cavities 
lined with typical or modified columnar epithelium and a stroma or 
reticulum of connective tissue. The amount of the latter and the ap- 
pearance of the cysts themselves vary in different cases. At times 
the stroma is very abundant and takes the form of well-organized fibrous 
tissue, while the cysts and acini are small and few in number. In these 
cases the appearance suggests a primary proliferative connective-tissue 
process with secondary implication of the epithelial elements. Such 
cases occur particularly in the mammary gland, and there is difficulty 
in separating them sharply from instances of chronic interstitial mastitis 
or diffuse fibroma. In other instances the process manifestly begins 
with the formations of epithelial acini, and the hyperplasia of the con- 
nective tissue is certainly secondary. The acini in these cases present 
themselves as hollow spaces of varying shape and size, often branching, 
and lined with columnar epithelium in a single layer or sometimes with 
several layers of more or less well differentiated columnar epithelium. 



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Nature. — These cystic growths often have a decided tendency to 
malignancy. They may remain benign throughout; but frequently 
they undergo carcinomatous change and spread widely or give rise to 
metastasis. The malignancy is generally in proportion to the amount of 
the epithelial proliferation and papuliferous change, but there are in- 
stances in which metastasis occurs from adenocystomata having regular 
gland acini lined with single layers of typical columnar cells. The cysto- 
mata of the ovary not rarely extend to the surface of the organ, break 
through the capsule, and present upon the surface as papillary growths, 
and frequently they extend to the peritoneum and neighboring struc- 
tures. The entire abdomen may be involved. At the same time, or in 
other cases independent of such direct extension, metastatic deposits 
may be seen in nearby lymphatic glands. Somewhat the same conditions 
may be observed in cystoma of the breast, but in this situation the tumor 
is much more frequently confined within the capsule of the organ. 



CHAPTER VII 



TERATOLOGY 

This subject includes all those abnormalities which are due to con- 
genital defect. Such a subject, while not exactly a part of the progres- 
sive tissue change, is ushered in here by the necessity of taking up cer- 
tain tumors having a polymorphous character more or less dependent 
upon formative defects. Teratomata or mixed or polymorphous tumors 
or those due to formative defect will first be considered, and the terata 
will then be discussed. The word "terata" may be applied to any ab- 
normalities of growth, but is best confined to monsters. In order to 
show the position of the various abnormalities we here give a short 
classification (Birnbaum's), which also indicates in a measure what we 
know of the etiology: 

(a) Single monsters. 

(1) Malformations due to arrest of development. 

(2) Malformations due to excess of development. 

(3) Malformations due to errors of development. 

(4) Malformations due to displacement of tissue and per- 

sistence of fetal structures. 

(5) Malformations due to fusion of several characters. 

(b) Double monsters. 

Two theories are given for monster formation. One is that there is 
some inherent fault in the germinal cell, and the other ascribes mal- 
formation to malign influences upon the developing ovum. The latter 
is more generally accepted. It is assumed that the damage is chiefly 
felt before the gastrula stage in a single ovum. 

Since all organs or organ systems do not progress to their develop- 
ment in a regular progression, but in an irregular saltatory manner, the 
correct development of any one depends upon the proper mutual 
relations of adjacent or associated units or groups. If, therefore, the 
progress and restraint of one unit be removed, this allows abnormal 
growth in those dependent upon it. In this way one can explain head- 
ings a, 1-3, 5; while the double monsters are expressions of the above 
effects upon a doubly impregnated ovum. Twins can arise from one 
ovum. 

TERATOMATA 

Definition. — The term "teratomata" is applied to tumors of peculiar 
mixed character, representing different elements of complex tissues 
or structures in a situation in which these do not normally occur, growing 
typically, atypically, or both. For example, the most frequent form of 

235 



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A TEXT-BOOK OF PATHOLOGY 



teratoma contains various epidermal structures, such as hair, teeth, 
etc., and occurs in internal organs. Those containing fetal tissue or 
abnormally placed tissue come under heading a, 4. 

Etiology. — The causation of teratoid tumors or teratomata is to 
be sought in congenital misdevelopments. We may, with Klebs, dis- 
tinguish endogenous forms in which inclusions of superficial tissues are 
retained in internal parts by a process of constriction; and eciogenous 
forms, in which a separate fetal deposition is the origin of the tumor. 
The latter form represents a separate and ill-developed fetus within 
the developed organism — a fetus in fetu. They are also called "em- 
bryomata." A regular gradation may be traced from distinct teratoid 
tumors having irregular mingling of tissue elements to malformations 
in which a more or less systematic outgrowth, somewhat approaching 
double monstrosities, occurs. Of the distinct teratoid tumors, the most 
frequent is the dermoid cyst. 

Dermoid Cyst 

This ectogenous tumor presents itself as a cystic formation with a 
connective-tissue membrane and an inner lining resembling the skin. 
This may present all the elements of the skin, such as stratified epi- 
dermis, a papillary layer, and even subcutaneous connective tissue. 
Hair-follicles and sebaceous glands are frequent, and habitually long, 
light-colored hairs are found within the contents, and teeth may be 
found in the lining membrane or free in the contents of the cyst. The 
cyst is filled with a semifluid, cheesy mass consisting of epithelial cells, 
fatty matter, and other detritus. Occasionally dermoid cysts may 
contain nerve tissue, muscle, thyroid tissue, or structures resembling 
intestine. 

The dermoid cysts vary in size from minute bodies no larger than a 
pea to huge masses, the latter being most frequent in the ovaries. 
Among the situations in which dermoids occur the ovaries are most 
common; less frequently they are found in the testicles, in the perito- 
neum, in the membranes of the brain, about the eye, in the neck, floor 
of the mouth, and elsewhere. Growth is very slow, and they may 
remain practically latent through life. 

The nature of these tumors is usually benign, though carcinomatous 
change may occur, and in the ovaries cystoma is prone to be associated, 
and the latter may be malignant. 

Other Teratoid Tumors 

Mixed tumors are terata arising from embryonal cells which are 
capable of a differentiation to approximate more than one type of adult 
tissue. They may descend from cells of one or all layers of the embryo, 
and may be ascribed to the power of syncytial cells to develop into an 
embryo, or the inclusion of one ovum in another. These are the tera- 
tomata proper, to which reference has been made, while mixed tumors 



TERATOLOGY 



237 



represent usually two or, at most, three types of cells. The most con- 
spicuous examples are Wilms congenital adenosarcoma of the kidney 
and adrenal carcinoma. 

Nodular masses may appear about the head or neck or in various 
parts of the body, consisting of mingled tissues of various kinds, such 
as glandular tissues, connective tissues, nerve, muscle, etc. Sometimes 
they resemble some definite organ, as in the case of growths appearing 
at the umbilicus of the newborn and simulating the structure of normal 
intestine. 

In the neck there are sometimes seen more or less cystic growths 
lined with epithelium and having in their walls muscle-fibers, lymphoid 
tissue, cartilage, etc. These growths probably spring from remnants 
of the embryonal branchial clefts. The mixed tumors of the parotid 
gland (see Sarcoma) are allied to these. 




Fig. 93. — Cholesteatoma from the membranes of the brain. 



Cholesteatoma. — This tumor is characterized by glistening, whitish, 
or pearly bodies composed of concentric layers of cells resembling epi- 
thelium (Fig. 93). Sometimes crystals of cholesterin are found in the 
center of these bodies, whence the name cholesteatoma. Cholesteato- 
mata are found in the membranes or substance of the brain, and present 
themselves as single or multiple nodules. They are usually soft and 
glistening in appearance. Some authors consider them endotheliomata, 
but Ziegler has found hair-follicles and hairs in certain specimens, 
and from this, as well as from the horny change to which the cells 
in the pearly bodies are prone, classifies them among the teratoid 
growths. They probably originate in ectodermal fetal inclusions or 
rests. 

Somewhat similar tumors occur in the pelvis of the kidneys, in the 
testicles, parotid glands, ovaries, and middle or external ear. 



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SYNCYTIOMA MALIGNUM 

This term is applied to a form of tumor originating at the placental 
site during pregnancy or the puerperium. It has also been called 
"deciduoma malignum," "sarcoma deciduocellulare," "destructive 
epithelial tumor of the placental site," and "chorionepithelioma" 
(Fig. 94). It may follow a hydatid mole (q. v.). 

The tumor occurs as a hemorrhagic infiltrating growth, somewhat 
resembling placental tissue in gross appearance, and frequently causes 
metastasis by breaking into the blood-vessels. The metastatic nodules 
are found in the external genitalia, frequently in the lungs, less often in 
the liver, spleen, or other organs. The growth is rapid, the uterine wall 




Fig. 94. — Chorionepithelioma or syncytioma malignum. (By the courtesy of Dr. Barton 
Cooke Hirst from a painting made for him from a slide belonging to Dr. Herbert Fox.) 

being quickly invaded and metastasis occurring in a short time. It 
has no vessels, but grows within placental blood spaces, and is prone to 
hemorrhage by infiltration and ulceration of maternal vessels. The 
cells are loosely enough arranged to separate and enter vessels to form 
metastasis. 

The nature of this tumor is still the subject of some controversy. 
Two types of cellular elements are recognized in its structure. One 
of these consists of irregular masses of protoplasm containing dark 
nuclei (syncytial tissue). The nuclei probably multiply by direct divi- 
sion. These protoplasmic masses are arranged in islands or in branch- 
ing columns which form a network. In the meshes of this network 
are blood spaces containing thrombi or masses of blood corpuscles. 
Sometimes masses like those above described are found within the 



TERATOLOGY 



239 



blood spaces. The second form of cells consists of smaller irregular- 
shaped elements, which are unusually rich in glycogen, and in which 
cell division by karyokinesis is observed. These cells lie in masses, of 
greater or less size, between and beside the larger protoplasmic areas 
before described. In the later stages of the growth obliterative throm- 
bosis of the vessels leads to necrosis of the cellular constituents, particu- 
larly of the columns of large epithelium-like cells. These are converted 
into homogeneous fibrinous masses, and even the thrombi themselves 
may degenerate. The view of Marchand regarding the nature of these 
tumors is most widely accepted. He holds that the larger cells are deriva- 
tives of the syncytium (a structure composed of epithelial cells, probably 
of fetal origin), while the smaller cells are formed from the deeper 
epithelial covering of the chorion villi (Langhans' cells). The tumor, 
therefore, is epithelial in nature, and it has malignant properties. It 
differs, however, from ordinary epithelioma and from carcinoma in its 
peculiar structure and in its clinical course and dissemination. 

Syncytial cells are occasionally found in tumors of the adult unasso- 
ciated with pregnancy. They are supposed to be either fused cells or 
to have a tendency to the formation of chorionic cells, possibly from 
germ cells. These cells have been found in brain and testicular 
growths. The name "syncytial carcinoma" or "epithelioma" is given. 

Terata or Monsters 

We refer the student to books on normal and abnormal embryology 
and teratology for a full discussion of the terata. Here will be given 
only examples of the various headings on p. 235 : 

(a) Single Monsters. — (1) Malformations by arrest of development 
are exemplified by the failure of closure of the median fissure of the body 
or the failure of union of organs developing in both sides and intended 
to be one, e. g., the bifid uterus. 

(2) Malformation in excessive development occurs in the form of 
supernumerary fingers or internal organs, the spleen, for example. 

(3) Malformations of error are seen in club-feet, hernia, or when 
the testicle is not included in the scrotum. Hermaphroditism exem- 
plifies failure of fusion of sexual elements from the two sides. 

(4) Malformation by displacement is exemplified by transposition 
of all the viscera (situs transversus) or of single organs, as when the 
heart is found on the right side. Persistence of a remnant of the 
omphalomesenteric duct, so-called Meckel's diverticulum, and of the 
trimcus arteriosus are instances of the retention of embryonal structures. 

(5) Under this heading are found fusion of esophagus and trachea, 
and of the two kidneys, forming a horseshoe-shaped organ. 

(b) Double monsters are the results of superfetation, or the fusion 
of incompletely formed fetuses. When the two fetuses are joined 
together by the ventral surface they are called anterior duplications; 
when joined by the head, craniopagus; by the sacral region, pygopagus. 
When they are fused at the pelvis they are ischiopagi; and if the trunk 



240 



A TEXT-BOOK OF PATHOLOGY 



and legs are fused, leaving the head and neck free, we have dicephalns. 
Syncephalus means fusion of heads with the two bodies free. 

The cysts of antenatal origin are mostly examples of endogenous, 
constriction, or inclusion cysts, or remains of fetal structures intended 
for removal. The thyrolingual cyst is due to failure of closure and 
obliteration of the thyrolingual duct. It is in the midline of the neck. 
Branchial cysts at the side of the neck are mucous or sebaceous collec- 
tions in the remains of the branchial clefts. Persistent portions of the 
Wolffian body or duct may give rise to uni- or multiloeular cysts of the 
ovary or broad ligament. Cyst sof the kidney are due to imperfect 
development of the portion of the Wolffian body which makes the 
secreting part of the kidney. 



CHAPTER VIII 



BACTERIA, THEIR NATURE AND ACTION 

History. — Although for many centuries there had existed the 
idea that disease and decay are due to the action of minute organisms, 
it was not until the use of the lens enabled the Dutch naturalist Leeuwen- 
hoeck actually to demonstrate their presence in water and in human 
intestinal contents that the hypothesis of a "contagium vivum" became 
more than mere guesswork. He discovered, even with his imperfect 
instruments, short rods, curved and straight, and described their 
motility. Miiller (1785), by the use of the compound microscope, at- 
tempted a more systematic classification of these micro-organisms, and 
from that time many investigators have added much to our knowledge 
of microbes, that group of organisms which had been denominated by 
Linnaeus by the term "chaos." To the German Henle is due the credit of 
having first introduced an idea of order into this disorder. He held that 
fermentation was the result of organic life, and that the action of a 
contagium was analogous to that of a ferment. The earliest systematic 
experimental work was that of Pasteur, in which he established beyond 
doubt this relation between fermentation and the life and development 
of bacteria. The first definite ideas of the physiology of these micro- 
organisms are found in his experiments on lactic-acid fermentation, 
and the pathogenesis of micro-organisms was established by his demon- 
stration of the etiology of the silkworm disease (1869). Davaine and 
Rayer about the same time established the causal relation of a bacillus 
found in the blood of a sheep dead of anthrax to that disease. 

CLASSIFICATION 

Bacteria (schizomycetes, or cleft fungi) is the name given to a \ 
branch of the lowest and simplest of the orders of the vegetable kingdom. 
They belong to the class Thallophyta and order Schizophyta or Schizomy- 
cetes. Other orders of this class are unimportant except the Eumycetes, 
comprising the moulds and yeasts. They are small, unicellular organ- 
isms, generally free of chlorophyl, and colorless; they possess a cell- 
membrane albuminoid in composition, and homogeneous protoplasmic 
cell contents. They range in size from a fraction of a micromillimeter 
up to 40 /x. Some varieties are motile. Nuclei are absent, though 
in the opinion of some the whole body may be regarded as a nucleus. 
Bacteria multiply by cell division, sexual distinctions being absent. 
In many species resistant bodies — spores — occur. 

Many classifications, all of them being to a certain extent artificial, 
have been made by different authors. Probably one of the most use- 
ful and scientific is that of Migula, as modified by Chester: 

16 241 



242 



A TEXT-BOOK OF PATHOLOGY 



Schizomycetes 

I. Coccaceae. — Spherical cells dividing in one, two, or three directions. Endospores 

rare. 

1. Streptococcus. — Division in one direction, the individuals cohering to form 

chains. Motility absent. 

2. Micrococcus. — Division in two directions, the individuals when coherent 

forming groups of four. Flagella absent. 

3. Sarcina. — Division in three directions, forming packets of eight, increas- 

ing in geometrical ratio. Motility absent. 

4. Planococcus. — Division in two directions, as in the micrococcus. Motility 

present. 

5. Planosarcina. — As the sarcina. Motility present. 

II. Bacteriaceae. — Rod-like, cylindrical cells, dividing at right angles to the long 

axis. 

1. Bacterium. — Cells without flagella, often with spores. 

2. Bacillus. — Cells with peritrichous flagella, often with spores. 

3. Pseudomonas. — Cells with polar flagella, spores rare. 

III. Spirillaceae. — Cells cylindrical, curved, bent, or spiral. Division as in II. 

1. Spirosoma. — Cells rigid, without flagella. 

2. Microspira. — Cells rigid, with one, rarely two or three, polar flagella. 

3. Spirillum. — Cells rigid, with five to twenty polar flagella. 

4. Spirocheta. — Cells flexible, motile, but without flagella; perhaps possessing 

an undulating membrane. 

IV. Chlamydobacteriacese. — Cells united in a simple unbranched filament. Division 

in one direction. Forms non-motile; conidia. 

1. Mycobacteriacew. — Short or long cylindrical units or filaments, clavate, cuneate, 

irregular, or regular in form; may have false or true branching. No spores. 
Gonidia bodies may occur; non-motile; transverse division; no sheath. 

a. Mycobacterium. — Short cylindrical, bent cuneate. May show true 

branching. 

b. Actinomyces. — Long branching filaments, gonidia, end organs, dry 

growth (very close to next genus, Streptothrix) . 

2. Streptothrix. — Cells united in a simple unbranched filament. Division in 

one direction. Forms non-motile; conidia, true branching. 

3. Cladothrix. — Cells united in a filament, with a false branching. 

4. Crenothrix. — Cells united in an unbranched filament, and dividing in three 

directions into small rounded cells. 

5. Phragmodiothrix. — Cells at first united in an unbranched filament, and 

dividing in three directions. Later the separate cells break through the 
thin membrane and grow out as branches. 

6. Thiothrix. — Cells united in an unbranched filament contained in a thin mem- 

brane. Division in one direction. Cells contain granules of sulphur. 

V. Beggiatoaceae. — Cells united in a filament without sheath. Motile, the move- 

ment being due to an undulating membrane. 

Eumycetes 

True fungi are of some pathological importance in skin diseases and occasion- 
ally in general infections. The classification is given of the most important genera. 
This is one of the orders of the Thallophyta. 

1. Suborder Phy corny cetes. 

Family Mucorinse, Genus Mucor. 

2. Suborder Hemiascomycetes. 

Family Saccharomycetacea?, Genus Saccharomyces, Subgenus Blastomyces. 

3. Suborder Euascomycetes. 

Family Aspergillacese, Genus Aspergillus, Genus Penicellium, Genus 
O'idium. 



BACTERIA, THEIR NATURE AND ACTION 



243 



The simple elementary forms that occur are of three kinds: the 
coccus, the bacillus, and the spirillum (Fig. 95). 

Coccus. — This is a spherical cell, varying in size up to 1 fi in diam- 
eter. It takes the anilin stains readily. Spore formation and motility are 
rare. When the cocci are found in groups, the individuals being entirely 
separate, they are termed staphylococci, from the resemblance of the 
groups to a bunch of grapes; when in pairs, diplococci; when in chains, 
streptococci; when in groups of four, tetrads, or merismopedia; when in 
packets, sarcinse. 

Bacillus. — A rod-shaped, cylindrical cell of varying length and thick- 
ness. Spore formation and motility are common. Most of the group 

. •: ! » • ■ >l & iiift 'ji /< 

1* 3 4 5 6 ? 'V* 9 ( » ii 

Fig. 95. — Various forms of bacteria: 1 and 2, Round and oval micrococci; 3, diplococci; 
4, tetracocci, or tetrads; 5, streptococci; 6, bacilli; 7, bacilli in chains, the lower showing 
spore formation; 8, bacilli showing spores, forming drumsticks and Clostridia; 9 and 10, 
spirilla; 11, spirochetes. 

stain easily with the anilin dyes, but some require special methods of 
staining. 

Spirillum. — A cylindrical, rod-shaped cell, curved or spiral, some- 
times motile. It stains readily. 

MORPHOLOGY 

Cell Contents. — The body of the organism in unstained conditions 
appears as a perfectly homogeneous protoplasmic mass. On staining 
with anilin dyes a granular appearance is often observed, which under 
high powers is resolved into a hyaline mass containing numerous 
chromophilic granules. Vacuolations also are often present. Some 
observers (Butsehli et al.) have made out a network immediately 
within the membrane and surrounding a central body which readily 
stains with the nuclear dyes. This latter they regard as a nucleus. 
Others, however, affirm that this appearance is due to a concentration 
of the cell protoplasm (endoplasm) , the result of the rather complicated 
method of staining. The question of the presence or absence of a nucleus 
is still an open one. In many organisms, as the diphtheria bacillus from 
a blood-serum culture, for example, there exist certain transparent re- 
fractive bodies which stain differently from the rest of the microbe. 
These metachromatic bodies, as they are called, are regarded by Ernst 
as nuclear in character. Others look upon them as possibly the primary 
stage of spore formation. 

Most authorities today merely accept that a bacterium has both 
chromatic and cytoplasmic parts, and do not insist that the large central 
area staining by nuclear methods is a definite nucleus. Some of the 
chromatic bodies seem to have the power of growing out into a full 
rod when freed from the parent rod into favorable media (Kneass). 



244 



A TEXT-BOOK OF PATHOLOGY 



Spore. — The spore is a non-vegetative resistant form that the microbe 
assumes when the conditions for growth are unfavorable. The endo- 
plasm seems to concentrate and become a small oval, highly refractive 
body, separated from the bacterial protoplasm by a membrane of its 
own. It is generally of the same diameter or somewhat smaller than 
the bacillus itself, and is situated either in the middle (equatorial) or 
at the end of the microbe (polar spore). It may be larger in diameter 
than the microbe and cause a swelling at that point. When in the center 
of the rod this gives rise to the form known as Clostridium; when polar, 
to the so-called drumstick form (as in the Bacillus tetani). 

The spore is extremely resistant to conditions to which the vegeta- 
tive form readily succumbs; to the action of certain chemical reagents, 
light, heat, etc. Bacteria that are grown on media poor in nutrient 
material tend to become asporogenous. A certain temperature is also 
necessary for spore formation. Thus, although the anthrax bacillus 
develops well at a temperature of 14° C. (57° F.), it does not form 
spores below 18° C. (64° F.). To obligate anaerobes oxygen is necessary 
for their development, and aerobic cultures present them in the ab- 
sence of that gas. Placed under conditions favorable to its vegetation 
the spore loses its clearness, absorbs water, and swells. A small promi- 
nence presents at the side or end, which gradually lengthens and develops 
into a young bacillus. The membrane of this new microbe is formed 
from the inner layer of the spore membrane (endosporium) , while the 
outer layer (exosporium) is cast off. In not all of the varieties of bacilli 
does sporulation take place, and even where it does occur there may, 
under certain conditions, as in growth at high temperatures, arise races 
which have lost this power (asporogenous races). 

The spore does not stain readily with the ordinary anilin stains, 
and special methods have been devised for coloring it. 

The polar or Babes-Ernst granules are condensations of endoplasm 
which stain by particular methods. They are due to the chemical 
reactions of the medium upon which the organisms are growing. Their 
biological importance is small, but they assist in identification at times. 

Cell=membrane. — Surrounding each organism is a membrane 
(ectoplasm) denser and more highly refractive than the cell contents 
(endoplasm). In most cases this is not to be differentiated from the 
endoplasm; but in a few it is larger, and under certain conditions be- 
comes a gelatinous mass. In this case it is easily seen, especially after 
appropriate staining. This is called the capsule. In general, this occurs 
only when the bacteria develop within the animal organism, and not 
upon artificial culture-media. It is probable that the ectoplasm is not 
a mere protective envelope, but has to do with the functional activity of 
the bacterium. The fact that the flagella, to which is due the motility 
of certain microbes, are directly continuous with and are simply pro- 
longations of this membrane, points to this view. 

The cell-membrane is not easily colored by ordinary methods. 

Flagella. — Motility is often a property of bacteria. It is manifested 
in different ways, and is often characteristic of special varieties of bac- 



BACTERIA, THEIR NATURE AND ACTION 



245 



teria. Some move slowly forward across the field; others, with great 
rapidity ; others, again, dart hither and thither, slowly or so quickly as to 
be with difficulty observed. They may at the same time have a rotary 
movement around their long or their short axes. 

After appropriate staining the cause of this motility is seen to be the 
presence of slender, whip-like prolongations, originating directly from 
the ectoplasm (Babes). They may be twenty times as long as the body 
of the bacterium, and are arranged in the different species in different 
ways. Bacteria that possess no flagella are termed "gymnobacteria" ; 
those that have these organs, "trichobacteria." There may be but one 
flagellum, situated at the pole (monotrichous), or a number may be 
present (lophotriehoits). When they are situated at both poles the microbe 
is termed amphitrichous; when distributed over the whole body of the 
bacteria, peritrichons. The presence and the activity of flagella depend 
on many factors: on the condition of the medium, bacteria grown on 
liquid media being more active than those on solid; on temperature; 
on presence of air; on light; and on the age of the culture. They are 
easily broken off from the microbe, and care must be used in staining 
them. 

Involution Forms. — By involution form is meant the irregular 
appearance a microbe often assumes when its conditions of growth are 
unfavorable. Numerous bacteria melt together and become irregular 
chains, or they appear pear or club shaped. The protoplasm becomes 
retracted and irregular staining takes place. Sometimes forms with 
branching projections are discovered. These have often been described 
as involution forms, but are now more commonly regarded as normal, 
though unusual, structures. This applies to tubercle bacilli, diphtheria 
bacilli, and some others. This true branching (dichotomy) must not 
be confounded with false or pseudodichotomy due to mere apposition of 
separate organisms, as seen in various bacilli, streptococci, etc., and 
habitually in the cladothrices. 

Chemistry. — The bacterial cells are of variable composition, de- 
pending to a great extent upon the kind of nutrient matter. They con- 
sist mainly of water (85 per cent.). The chief solid material is albumin. 
This varies according to the medium of growth, and has been given the 
general name of mycoprotein (Xencki). Fat is also present. The nuclein 
bases — xanthin, guanin, adenin — and cellulose have been found by some. 
Some contain certain coloring-matters, bacteriopurpurin, and a green 
substance similar to chlorophyl. Organic acids and ferments of differ- 
ent kinds are also found. In some special forms — the sulphur bacteria — 
sulphur is present. 

BIOLOGY 

Bacteria may be divided into two great classes: those that live only 
on dead organic matter are termed saprophytes; those that develop in and 
at the expense of the living organism, parasites. These latter by their 
growth cause certain pathological conditions in the host, and are called 
pathogenic. By obligate saprophytes or parasites we mean those that 



246 



A TEXT-BOOK OF PATHOLOGY 



can exist only under the conditions named; by facultative saprophytes 
or parasites, those that can develop under either condition. 

Conditions of Growth. — Certain surrounding conditions are neces- 
sary to bacteria, and any marked change in them will inhibit the growth 
or totally destroy it. 

Mechanical Conditions. — A slight shaking of a liquid culture 
seems to help the development of bacteria, while a more violent and 
long-continued agitation destroys them. 

Physical Conditions. — Electrical currents destroy the growth, prob- 
ably by the action of certain products of the electrolysis and not by 
direct action. 

Light. — Diffused daylight inhibits the growth of bacteria: sunlight 
and, to a less extent, electric light destroy them. This is probably due 
to oxidation. 

Heat. — A certain temperature is necessary, the degree varying with 
the species of microbe. Most of the water bacteria and saprophytes 
grow between 0° and 30° C. (32° and 86° F.), the optimum being 15° to 
20° C. (59°-68° F.) (psychrophilic). The pathogenic flourish between 
10° and 45° C. (50° and 113° F.), best at the body temperature, 37° C. 
(98.6° F.) (mesophilic) . There are some that develop well at 40° to 
70° C. (104°-158° F.) (thermophilic). Above these limits the members 
of the several groups are killed, and each bacterium has its own thermic 
death-point. That of most of the pathogenic varieties lies between 
50° and 60° C. (122° and 140° F.). Below the lower limit, down to the 
degree at which any multiplication will occur, the growth is inhibited 
only. Temperatures below zero destroy only the most feeble of para- 
sites. Very low temperatures (—250° C; —418° F.) have been used 
without preventing the future development of the microbe. 

Spores are extremely resistant to higher temperatures. While 
no bacterium can live after exposure to 100° C. (212° F.), the spores of 
some of the earth microbes are killed only after exposure for an hour to 
steam heated to 115° C. (239° F.). 

Chemical Conditions. — The essential substances for the growth of 
bacteria are water, carbon, nitrogen and oxygen, and certain salts. 
For the carbon, they require already prepared carbon compounds, as the 
sugars, glucose, saccharose, lactose, etc., mannite, glycerin — in fact, 
most of such as are soluble in water. Most of the proteins and many 
simpler substances, even such as ammonium carbonate, furnish the 
nitrogen. Free oxygen is necessary for many microbes. Those for 
which this is absolutely required are termed "obligate aerobic." Facul- 
tative aerobes are those that grow best in the presence of oxygen, but 
may develop in its absence. Anaerobic microbes are those that grow 
best without atmospheric oxygen and are also obligate and facultative. 
They obtain it as they need it by reducing oxygen-containing materials 
in the culture-medium. It has been found possible to produce races 
which, although naturally obligate anaerobic, develop also in an atmos- 
phere of oxygen. 



BACTERIA, THEIR NATURE AND ACTION 



247 



FUNCTIONS AND PRODUCTS OF BACTERIA 

The study of the substances that result from the action of the life 
of bacteria and the changes that they produce in their various media 
of growth is really a branch of organic chemistry. The function of 
bacteria is essentially a destructive one. They split up the higher 
nitrogenous and non-nitrogenous compounds into simpler substances. 

The various substances that are found in cultures of bacterial 
growth comprise: (1) the components of the bacterial cell proper, as 
the proteins; (2) the secretions of the cell, as the ferments and toxins; 
and (3) substances that are the result of the action of microbes upon 
the medium of growth. The toxic substances in bacterial cultures may 
be classed as (a) intracellular and (b) extracellular, according as they 
are contained within the bacterial cell or are made from or excreted 
into the culture-medium. The extracellular substances may be purely 
products of bacterial secretion which have been separated from the 
cell, or they may be decomposition products derived from the culture- 
medium. 

The bacterial proteins may produce suppuration (pyogenic) or fever 
(pyrogenic) , or they may be the cause of an inflammatory process (phlogo- 
genic). These substances are comparatively resistant to heat and are 
thus sharply distinguished from the ferments and toxins. The best- 
known examples are mallein, derived from the bacillus of glanders, 
and tuberculin, from that of tuberculosis. These are pyrogenic when 
injected into animals suffering respectively from glanders or tubercu- 
losis, biit have no, or at least very slight, effect upon healthy subjects. 
Other proteins are shown to have similar effects on tuberculous animals, 
but not in the minimal doses which suffice when tuberculin is used. 

Vaughan and his associates claim that the protein of bacteria is 
divisible into a highly toxic non-specific portion, and a non-toxic 
fraction specific for each kind of organism. Upon this result and his 
further experimentation he has elaborated a theory of infection to be 
discussed later. The endotoxins are certainly closely bound with the 
bacterial proteins, but their exact seat is not known. 

The second group of products includes the ferments and possibly 
the toxins. 

Ferments. — A ferment is a complex body about which we know 
but little except the effects that it produces. By its presence, and 
probably without entering into intimate chemical combination^ it pos- 
sesses the power of breaking up more highly organized nitrogenous 
and non-nitrogenous compounds into simple and more diffusible mole- 
cules. They are termed enzymes or unformed ferments in contradistinc- 
tion to the bacteria themselves, which are called formed or living fer- 
ments. That the action of ferments is not due directly to the microbe 
is shown by the facts that bactericidal substances, such as phenol 
(5 per cent.), chloroform, ether, etc., have no effect on them, and that 
cultures freed from bacteria by filtration still possess fermentative 
power. The action of ferments is termed fermentation, but this term 



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A TEXT-BOOK OF PATHOLOGY 



is more especially limited to the effect of certain ferments upon non- 
nitrogenous compounds, particularly the carbohydrates. The result 
of fermentation upon nitrogenous material is called putrefaction, which 
generally occurs with, though often without, the formation of odorous 
gases and other substances. The intracellular origin of certain ferments 
has been demonstrated by their experimental separation from the 
bacteria when placed under high pressures. The resulting bacteria- 
free liquid possesses the same fermenting qualities as the culture 
itself. 

The ferments, like toxins, are of unknown composition, are highly 
destructible by chemical agents and heat, cause effects out of all pro- 
portion to their bulk or amount, and are frequently mechanically 
precipitated with various indifferent bodies. When injected into ani- 
mals both are capable of exciting the formation of antibodies (anti- 
ferments and antitoxins). 

Bacteria, as animal cells, have autolytic ferments. In this self-solu- 
tion certain substances are freed that may be of importance in immunity 
reactions — endotoxins and aggressins. The exact relation of bacterial 
digestion products, whether autolytic or by the agency of blood-serum 
or tissue fluids, is not exactly known. The demonstrable enzymes of 
bacteria have little to do with the specific infection caused by the 
growth aside from the softening of exudates and the like. This ex- 
ample is given to show also that one of the most important enzymes 
of bacteria is proteolytic in action. 

The principal bacterial ferments are: 

Proteolytic Ferments. — These transform albumins into more soluble 
and diffusible substances. One form very often met with is that which 
liquefies gelatin. This acts in an alkaline medium, and is, therefore, 
akin to the animal ferment trypsin. This liquefaction of the gelatin 
affords a means of distinguishing many species of microbes. 

Diastatic Ferments. — These transform the starches into sugars, 
and are found in many bacterial cultures, as of Bacterium mallei, B. 
pneumoniae, etc. 

Inverting Ferments. — These change the non-fermentiscible sugars 
into those that undergo direct fermentation. Such ferments are found, 
for instance, in cultures of Spirillum cholera and S. metschnikovii. 

Coagulating Ferment. — One of the means of differentiation of 
bacteria is the coagulation of milk used as a culture-medium for the 
bacteria under observation. This coagulation is due not to acidity 
produced in the medium, but to the action of a ferment. 

Some varieties of microbes produce a ferment that has the power 
of dissolving this coagulum when formed (casease); and still others 
produce both ferments — the coagulating and the dissolving. 

Hydrolytic ferments are exemplified by such as break up urea 
into ammonium carbonate and hippuric acid into glycocol and benzoic 
acid. 

Fat-splitting ferments split the fats into glycerin and the fatty acids. 
Oxidizing and nitrifying ferments are other less important forms. 



BACTERIA, THEIR NATURE AND ACTION 



249 



Effects of Ferments. — The single or combined action of these 
various ferments causes certain special kinds of fermentation distin- 
guished by the principal substance produced. Alcoholic, lactic acid, 
and butyric acid fermentation of the sugars, acetic acid fermentation of 
alcohol (Bacillus acidi lactici, B. bidyricus, B. acidi butyrici, etc.); cellu- 
lose fermentation with the production of carbonic acid gas and ammonia ; 
nitrification, in which oxidation of ammonium leads to production of 
nitrates (Winogradsky's nitrosomonas), and secondarily conversion of 
nitrates into nitrites (nitrobacter) ; mucoid fermentation of glucose and 
invert-sugar are examples. 

Toxins. — The pathogenic bacteria produce certain toxic substances 
that are akin in action to the poisonous venom of certain serpents and 
other animals, and to certain poisonous principles of plants, as abrin 
and ricin, and are almost certainly of protein nature. These are of in- 
definitely determined character, and act deleteriously upon the host 
only after the lapse of a certain time — a period of incubation. They 
are considered the specific toxins of the several bacteria. According to 
some, these give all the reactions of albumin, and have been termed 
toxalbumins (Brieger). It is probable, however, that the toxalbumin 
is but an impure form of the true toxin, a combination of it and various 
substances derived from the medium of growth. Most recent investiga- 
tors look upon the toxin as akin to the ferments. Roux and Yersin, in 
their monograph on the diphtheria bacillus, held this view and more 
recent investigators support the theory. The analogous pathological 
action of the toxins and ferments, their common origin, their destruc- 
tion (oxidation) in the presence of light, their precipitation by alcohol, 
their precipitation from solutions by colloid bodies, their long and im- 
perfect dialvsis, all point to this. High temperatures affect both similarly, 
both being destroyed at from 60° to 100° C. (140°-212° F.). Chemical 
substances that have no effect (chloroform, ether, etc.) on the ferments 
are without action upon the toxins; and, vice versa, those that destroy 
the ferments (formaldehyd) are also injurious to toxins. They are, 
curiously enough, digested by proteolytic ferments. Both may be 
swallowed with impunity, although they are pathogenic when injected 
subcutaneously or intraperitoneally. ^Yhen the microbe is grown 
in some inorganic medium or in a non-albuminous one (as Uschinky's 
solution), the toxic principle obtained corresponds in its chemical reac- 
tions to a ferment. Most important is the fact that extremely minute 
doses are effective. Ferments act without regard to the mass em- 
ployed, and it would seem that toxins act in almost imponderable 
amounts. It has been estimated that two gm. of tetanus toxin will 
kill a horse weighing 600 kg. — six hundred million times its weight; and 
that two" tng. of tuberculin causes a reaction in a diseased man weigh- 
ing 60 kg. — sixty trillion times its weight. Finally, both act only after 
a definite period of incubation. 

Considerable light has been thrown upon the nature of toxins by 
the recent investigations of Ehrlich and others who have followed 
him. These investigations have been mainly concerned with the 



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A TEXT-BOOK OF PATHOLOGY 



behavior of the toxin toward the antitoxin bodies. Ehrlich has found 
that the serum contains at least three distinct substances: the toxin 
proper, toxoid, and toxon. The toxin is the active poisonous element; 
but, aside from its toxic property, it has a distinct combining ability, 
so that it enters into combination with antitoxin. A given serum, how- 
ever, will combine with a greater quantity of antitoxin than the toxic 
power of the serum would indicate. In other words, there are other 
combining bodies which have no toxic power, or less toxicity than the 
toxin. A serum as it grows older loses in toxic power without losing in 
combining power. This is due to the conversion of toxin into toxoid. 
The toxon has, similarly, the combining power for antitoxin, but is 
slightly toxic, being capable, in the case of diphtheritic serum, for ex- 
ample, of producing the postdiphtheritic paralyses. It is, however, not 
a derivative of the toxin, but results from a direct action of the bac- 
terium, and is produced simultaneously with the toxin. The dissocia- 
tion of combining power and toxic power is explained upon the assump- 
tion that each molecule of toxin contains a group of atoms specially 
adapted for combining with vulnerable cells or with antitoxin and a 
toxic group. To the former the name haptophore group and to the 
latter the term toxophore group has been given. The probable nature 
of these will be referred to in the discussion of Ehrlich's theory of im- 
munity. 

Fate of Toxins. — It is certain that there exist in various cells of the 
animal organism certain oxidizing ferments by which the toxin is de- 
stroyed. Not all of the toxin is thus oxidized. A part is eliminated 
unchanged through the kidneys in the urine and to some extent through 
the liver in the biliary secretion. Besides these there is still another 
method of defence of the organism against the action of toxin — the 
antitoxin (q. v.). 

PRODUCTS IN CULTURE-MEDIUM. 

The third group of poisons found in bacterial cultures are the 
products of decomposition of the culture-medium under the influence 
of the bacterial growth. This is the class of poisons called ptomains, 
protein degradation bodies, with their nitrogen in the amino form. 
They act as a direct poison and require no specific incubation period. 
They differ from toxins in the fact that their elaboration is more closely 
dependent on the character of the medium than is that of the former. 
The toxin of tetanus or diphtheria may be produced in various, even in 
non-albuminous, media, but the elaboration of certain ptomains and 
other decomposition products is more narrowly restricted ■ to growth 
of certain organisms in appropriate media. The substances produced 
by bacteria from the culture-media and tissues are varied and numerous. 
Besides those produced by the various fermentative processes there 
are: the products of digestion of albumin, albumoses, peptone, etc.; the 
ptomains; nitrogenous substances, as leucin and tyrosin, methyl-, di- 
methyl-, ethyl-propylamins; organic fatty acids, formic, acetic, propionic, 



BACTERIA, THEIR NATURE AND ACTION 



251 



butyric, margaric, lactic, etc.; certain aromatic compounds, as indol, 
phenol, kresol, skatol, mercaptan, hydrochinon, etc.; and finally, hydro- 
gen, carbonic dioxid, hydrogen sulphid, ammonium, water, etc. All 
of these are more or less toxic and may contribute to the unfavorable 
action of bacteria, but are not the specific toxic agents that occasion the 
characteristic pathological effects of the various micro-organisms. 

Chromogenesis. — Many bacteria form colors which give to the 
culture a characteristic appearance. The production of the pigment 
depends to some extent upon the constitution of the medium, and it is 
possible to produce cultures and even races of pigment-forming bacteria 
by the use of appropriate media. It has no importance in the patholog- 
ical relations of the organisms. 

Photogenesis. — The phenomenon of phosphorescence observed 
in decaying fish is due to the action of bacteria. This production of 
light is observed in many of the cholera group of vibriones. 

THE LOCAL EFFECTS OF BACTERIA 

These may be either (a) mechanical or (b) histological, the mechanical 
effects being least in importance, (a) Sometimes masses of micro- 
organisms more or less completely occlude small blood-vessels and 
occasion secondary changes in the tissues in this mechanical way. In 
other cases the obstruction is incomplete, but occasions thrombosis in 
the blood-vessels and various consequential disorders, (b) The histo- 
logical changes occasioned by bacteria are proliferative and destructive, 
among the latter being various degenerations and necrosis. The pro- 
liferative changes may be non-specific or specific — that is, there may be 
simply proliferation such as occurs from any irritation ; or there may be 
special forms of proliferation more or less characteristic of the individual 
micro-organism in extent, distribution, and nature. This is seen in the 
peculiar lesions of tuberculosis, glanders, rhinoscleroma, etc. The 
cellular degenerations and necroses occur coincidentally or subsequent to 
the proliferative changes. On the contrary, in many cases the first 
effects of bacterial invasion seem to be degeneration or necrosis of the 
tissues immediately around the organisms. 

EFFECT OF TOXIC PRODUCTS OF BACTERIA 

This section of the subject is devoted to a consideration of the 
modus operandi of the foregoing bacterial products upon the body. 
The general principles apply to protozoan and metazoan parasites, but 
we deal here chiefly with bacteria. The action of all the animal parasites 
is not understood, and comment upon them will be reserved for the 
appropriate chapter. 

Infection is the successful invasion of the tissues by bacteria and the 
evidences of their presence. Infestation is the term applied to the 
presence and action of animal parasites within the body. 

The sources of infection (here and throughout this chapter we use 



252 



A TEXT-BOOK OF PATHOLOGY 



the term very broadly) are polluted objects — food, water, and insects. 
The action of each will be described when discussing the diseases to which 
they apply. This is the principal subject of hygiene and should be 
studied in works devoted to it. 

It must not be forgotten that bacteria, even some pathogenic forms, 
are constantly present upon and within the human body. They are 
held in abeyance or destroyed by the primary defenses — the skin and 
mucous membranes. Should a lowering of these defenses or a great in- 
crease in the invasive powers of the bacteria occur, infection follows. 
The character of the infection depends somewhat upon the portal of 
entry or so-called infection atrium. Typhoid bacilli will not produce 
typhoid fever if rubbed upon the skin, but may if swallowed. Pus 
cocci may cause furunculosis if rubbed upon the skin, but will not if 
swallowed. 

All openings to the body present possible infection-atria, and pre-exist- 
ing disease of any part lowers the resisting powers of that part in par- 
ticular and possibly of other parts. The most important infection-atria 
are the respiratory and alimentary tracts. Bacteria are inhaled or 
swallowed and lodge upon the mucous membranes. As has been said, 
these membranes are part of the primary defenses, but it has been shown 
that bacteria may pass them without leaving a trace. The invaders 
are met then by the resistance of the lymphatic system in which they 
are carried through the lymph-channels, or by the antibacterial power 
of the blood. 

Pathogenicity is the power of the germ to produce disease. This 
does not always run parallel with virulence, as will be seen in the sub- 
acute infections. The power of the germs to resist the bodily defenses 
and, by their extra- or intracellular poisons, to produce a pathological 
effect, is their virulence. Ehrlich explains virulence by the statement 
that a bacterium is virulent to the extent that it has haptophorous or 
binding receptors to bind and sidetrack the defensive receptors of the 
body tissues. (See pp. 262, 263, and Immunity.) 

An attractive theory has been suggested by Bail to explain the 
unusual virulence of micro-organisms under certain circumstances. 
It was found by Koch that intraperitoneal inoculation with fresh cul- 
tures of tubercle bacilli causes a rapid destruction of tuberculous ani- 
mals. Bail found that if tubercle bacilli and sterilized tuberculous 
exudate were injected into healthy animals, sudden death resulted. 
Neither the sterile exudate nor the tubercle bacilli alone had such an 
effect. He, therefore, assumed that something in the exudate increases 
the virulence of the micro-organisms and gave the name "aggressin" to 
the hypothetic substance. The exudate found in the peritoneal cavity in 
these cases was found to consist solely of lymphocytes, and Bail suggests 
that the aggressin acts by paralyzing the polymorphonuclear leukocytes 
and thus prevents phagocytosis. The lymphocytic character of tuber- 
culous exudates is explained by the presence of the aggressin in the tuber- 
culous animal or man, and the consequent prevention of migration of 
polymorphonuclear leukocytes. Similar phenomena have been found 



BACTERIA, THEIR NATURE AND ACTION 



253 



in cases of other micro-organisms. Anti-aggressins have been produced 
by repeated inoculation of animals with exudates containing the aggres- 
sins. 

Some bacteria or their toxins have a predilection for certain tissues, as, 
for example, tetanotoxin for the nervous system. This and other 
phases of virulence will be considered under Immunity. 

The probability of a successful infection varies directly with the 
number of organisms introduced, the virulence of the invaders, and 
with the resistance offered by the individual. 

Intoxication and Infection. — In one class of diseases the in- 
fecting microbe remains localized at the point of inoculation, and is 
never or only exceptionally found in the fluids of the body, the general 
symptoms of the disease being due to absorption of the toxic products. 
In such cases the general symptoms of the disease are true intoxica- 
tions. In other cases the microbe is found circulating in the blood 
throughout the body and finds lodgment in most of the organs. These 
are called infections in the strict sense. Tetanus is the type of the 
first class; anthrax, of the second. There is, however, no distinct line 
to be drawn, for the symptoms of all infections are doubtless due to 
toxins or other toxic products, whether produced locally at the point of 
implantation of the organism or throughout the body when it is dissem- 
inated. The distinction between intoxication and infection depends 
upon the method of toxin production. 

The intoxications form a small class, of which diphtheria, tetanus, 
and botulism are the only practically important members. These 
diseases are due to extracellular poisons, commonly called toxins, 
which are made from the medium upon which the bacteria are living. 
For example, diphtheria bacilli growing on the pharynx pervert the 
normal bodily protoplasm to a toxic form. The toxin is negative, or 
at least antichemotactic (see Inflammation), and thus prevents the 
phagocytic action of the leukocytes; while most other bacterial products 
and the bacterial proteins are positively chemotactic. 

The second class, the infections, is much larger. While it is possi- 
ble that a modicum of extracellular poison is formed by microbes 
causing infection, it is certain that by far the greater amount is not 
available until the bacterial body is digested and the protoplasm lib- 
erated (endotoxin). The lysis of the germs may be focal or in the 
circulation, in either case due to the bacteriolytic power of the blood 
or to phagocytosis. Under Immunity and Allergie theories of the 
pathological action of these toxins will be discussed. 

A virulent microbe is one that invades the animal body and there 
produces its more or less powerful toxin; an avirulent one produces but 
little, if any, toxin, and is destroyed by bacteriolytic substances and by 
phagocytosis, either with or without suppuration. The number of or- 
ganisms, as well as the virulence, is important in determining the char- 
acter of the effects. 

Sapremia, Septicemia, and Pyemia. — From local suppurative 
foci, or necrotic areas due to saprophytic or non-virulent germs, toxic 



254 



A TEXT-BOOK OF PATHOLOGY 



products may be absorbed into the general circulation, and a con- 
dition known as sapremia results. The infecting bacterium itself may 
invade the blood-current without giving rise to any secondary lesions. 
This is termed septicemia. When, however, the microbe is carried to 
various parts of the body and there gives rise to secondary suppuration, 
the condition is called pyemia. Bacteremia is a term that may be 
used to indicate merely the circulation of bacteria in the blood with- 
out implying any clinical condition. 

Infections may also be divided into fulminating, acute, chronic, and 
Adami's subinfection. 

Fulminating infections are sudden overwhelming attacks by bacteria, 
in which all bodily defenses are destroyed and death results before new 
defenses can be raised. 

Acute infections are those manifested by a short clinical course of 
more or less definite type and are the evidences of a brief depression of 
bodily defenses. They tend to be self-limited. 

Chronic infection is the expression of struggle between the disease 
agent and bodily defenses over a long period and without definite stages. 
Tuberculosis is typical of such a disease. 

Between this and the second form there is another, called variously 
subacute and chronic remittent. This may be a continuation of an acute 
condition or arise insidiously and cryptogenetically . The cases have 
constantly some evidences of infection, but are subject to remissions, 
acute in form, followed by disappearance of the more evident signs of 
infection when the exacerbation has passed. In cases studied by us 
there is persistent bacteremia. The cause seems to lie in a condition 
of balance between the bodily defenses and the bacterial offenses. 
Sometimes we have found that the failure of defense is on the part of the 
leukocyte; at others, on the part of the serum. The bacteria in these 
cases are in a condition known as "fast" or "fixed." We can only 
state that they seem to have immunized themselves in some way against 
the bodily defenses, and in so doing do not give rise to new defenses or 
antibodies. The bacteria may be considered as possessing a fairly well- 
marked pathogenecity, but a low virulence. 

Subinfection, according to Adami, is a condition of repeated infec- 
tion from the bowel or respiratory tract due to congestion or mild 
inflammation. These changes enable bacteria or their products to 
pass to the lymph or parenchymatous organs, where they are de- 
stroyed, their remains being found as amorphous granules resembling, 
but distinguishable from, pigment. The effect is that of continued or 
repeated irritation, and Adami believes they are factors in the production 
of cirrhosis and anemias. The focal infections of some writers belong in 
the subinfections. 

Mixed Infections. — This is a state in which the effect of one agent is 
superimposed upon another, with usually an intensification of the symp- 
toms or a rendering of them slightly atypical. 



BACTERIA, THEIR NATURE AND ACTION 



255 



IMMUNITY 1 

Definition. — In the present state of our knowledge of the condi- 
tion of immunity it is most difficult to give a precise definition of this 
term. It denotes that condition of an organism which enables it to 
resist the attacks of bacteria and their toxic products. In one sense 
it is the reverse of susceptibility. An animal that is not susceptible to 
an infection is said to be immune, and the term "immunization" is ap- 
plied to the process by which an animal becomes thus refractory. 

Varieties. — Two principal forms of immunity, with a number 
of subdivisions, are recognized: (a) Natural immunity; (b) Acquired 
immunity. 

(a) Natural immunity is the power of resistance to certain bacteria 
and toxins manifested by races or classes of men and animals, or even by 
certain individuals. It is always or nearly always an inheritance from 
immune ancestors, and can readily be accounted for on the principles 
of heredity. We may distinguish: 

1. Natural Bacterial Immunity. — In this case the resistance is 
offered to some specific bacterium. Thus, none of the lower animals is 
susceptible to naturally acquired syphilis, measles, or leprosy; man is in- 
susceptible to rinderpest; dogs and Algerian sheep, to anthrax; chickens, 
to tetanus; and in epidemics of various kinds some individuals regularly 
escape. This bacterial immunity 2 is only exceptionally absolute; usually 
it is merely relative, the susceptibility or insusceptibility varying with 
the environment or individual conditions. 

2. Natural Toxin Immunity. — Just as the hog is naturally resistant 
to snake-venom, so certain animals are immune to certain bacterial 
toxins. Rats are resistant to diphtheria toxin; chickens, to tetanus 
toxin, etc. 

(6) Acquired Immunity. — This may be naturally acquired, as when an 
animal has passed through an infectious disease; or artificially acquired, 
when an animal or man has been inoculated with bacteria or bacterial 
products. We may again distinguish two subvarieties, as in the case 
of natural immunity: 

1. Acquired Bacterial Immunity. — In this form the animal or man 
has been rendered immune by previous naturally acquired disease, or 
by inoculation with the specific organisms that have been first reduced 

1 Certain definitions and synonyms must be understood to read properly this and 
other articles on immunity: 

Antigen, or exciting substance, is the bacterium cell or substance used for immu- 
nizing to produce antibodies; these, then, are substances formed against antigens. 
Toxin, ferments are the soluble products of disease agents. 
Toxophore, the poisonous or intoxicating fraction of an antigen. 
Haptophore, the binding fraction of antibody or antigen. 

Complement, c.ytase, alexin, the normal thermolabile antisubstance in blood-serum. 
Zymophore, the toxic radical in agglutinins and precipitins. 
Cytophile fraction of antibody combines with cells. 
Complementophile fraction of antibody combines with complement. 
Immune body, amboceptor, intermediate body, fixateur, substance sensibilisatrice, prepara- 
teur, copula, and desmon are synonyms for the thermostabile body raised against antigens. 

2 The various immunities of animals are not always absolute under experimental con- 
ditions. It is possible to give monkeys and, probably, rabbits syphilis, but they do not 
have syphilis as an endemic among them ; it is not natural to lower animals. 



256 



A TEXT-BOOK OF PATHOLOGY 



in virulence or killed by heating and other means. Acquired bacterial 
immunity does not follow all infections. In the case of gonorrhea, 
for example, it is wanting; and in erysipelas there seems to be increased 
susceptibility; but in most of the infections immunity is produced. 
It is of variable duration, sometimes lasting throughout life, some- 
times only brief periods of time. 

2. Acquired Toxin Immunity. — In this form the immunity is 
produced by the injection into animals of the toxins from bacterial 
cultures, or by injection in men or animals of serum of animals that 
have been rendered naturally or artificially immune. 

The terms "active" and "passive" are used in connection with types 
of immunity to designate the active or passive part taken by animals 
or men in the acquirement of the immunity. 

Active Acquired Immunity. — This term is applied when artificial 
bacterial immunity or toxin immunity has been produced by inocula- 
tion with living or dead bacteria or by injection of filtrates of cultures, 
because in these cases there is active production of the immunizing sub- 
stances in the body of the experimental animal. 

Passive Acquired Immunity. — This term is applied to the protec- 
tion afforded by injections of serum of immune animals, because in 
this case the process is passive as far as the recipient of the antitoxic 
injection is concerned. Active immunity is relatively much more last- 
ing than passive. 

In many cases immunity asserts itself against both the infecting 
microbe and its specific toxin, as in the rat with regard to the diphtheria 
bacillus and its toxin; but more often an animal is resistant to the 
infection, though susceptible to the toxin. An example of this is the 
action of the guinea-pig toward tetanus (Vaillard). The reverse may 
be true, and we see an injection of tuberculin without effect upon a 
healthy animal that is very susceptible to tuberculous infection. Most 
commonly natural immunity exists toward the infecting microbe and 
not its toxin. 

Theories of Immunity. — All the phenomena of immunity have not 
been satisfactorily explained, but the subject is at least much clearer 
than formerly. 

Bacterial Immunity. — Alexin Theory. — The blood-plasma and 
fluids of a naturally immune animal are capable of destroying the 
bacteria toward which the animal is immune. That the destructive 
agent is contained in the blood itself is shown by the fact that the 
defibrinated blood and pericardial effusions of dogs and rabbits destroy 
anthrax bacilli outside the body. This bactericidal action is not, how- 
ever, specific nor confined to serum from animals naturally immune 
to certain infections. On the contrary, the destructive action is mani- 
fested toward all micro-organisms in varying degrees, and the serum 
of man or animals always manifests bactericidal power, though not al- 
ways decidedly. This bactericidal action was attributed by Buchner to 
certain albuminous bodies which he termed "alexins." These are unstable 
substances resembling ferments in action and easily destroyed by heating 



BACTERIA, THEIR NATURE AND ACTION 



257 



the serum to from 55° to 60° C. (131°-140° F.). It has been recently 
shown that the protection in bacterial immunity is not afforded by a 
single body or alexin, but by two distinct substances, each of which is 
necessary. (See Ehrlich's Side-chain Theory.) 

Phagocytosis. — Metschnikoff proposed the very attractive theory 
of phagocytosis. He has, however, modified his older views because of 
new experimental work along the lines laid down by Ehrlich. He now 
maintains that phagocytosis is the principal factor in immunity and that 
soluble immune bodies in the plasma are derived from leukocytes. 
Even extracellular digestion of bacteria is due to substances from leuko- 
cytes. The infecting microbes are taken up by certain cells of the 
organism and are destroyed by intracellar digestion, or are dissolved by 
ferment-like bodies derived from phagocytes when they break (phago- 
lysis). These cells — phagocytes — are of two kinds: the microphages, 
including the polymorphonuclear leukocytes; and the macrophages, in- 
cluding mononuclear leukocytes, the vascular endothelial cells, cells of 
the bone-marrow and spleen, certain connective-tissue cells and Kup- 
fer's cells, and even those of the nerve and muscle tissue. The micro- 
phages are mainly concerned in the absorption and destruction of bac- 
teria; the macrophages, in the destruction of cells, portions of dead tis- 
sues, and the like. After injection of a culture into the subcutaneous 
tissue of an animal naturally or artificially immune, he noticed that 
the bacteria were all taken up by the leukocytes. That these microbes 
were still living and virulent, and were not taken up as mere dead matter, 
Metschnikoff regards as fully established. One proof he cites is the 
fact that an exudate containing no free bacteria, but all intracellular, 
is capable of producing cultures on artificial media and causing infection 
in susceptible animals. The ferment freed by disintegration of phago- 
cytes Metschnikoff called "cytase." 

Certain important features of Metschnikoff 's theory and results must 
be emphasized. Increase of resistance to bacteria is usually associated 
with an increased phagocytic power, but not always, and occasionally 
an infection, during which the blood and leukocytes possess high pha- 
gocytic power, results fatally. In some infections an immunity results, 
although w T e cannot perceive any change in the leukocytes. It has not 
been proved that antibodies arise from phagocytes. The cellular theory 
of Metschnikoff is not incompatible with the humoral or side-chain 
theory of Ehrlich, but merely explains certain phases of immunity 
reactions. The phagocytes are, undoubtedly, very important bodily 
defenses. One of the most difficult phases to explain in terms of this 
theory is the mechanism of the ill-understood increase in virulence. 
Organisms are resistant to phagocytosis directly as virulence changes, 
yet it is possible to get an immunity to a virulent organism without 
phagocytic action. 

Bacteriolytic Theory. — Pfeiffer opposed to Metschnikoff 's theory 
the experiment of injecting cholera vibriones into the peritoneum of 
artificially immunized guinea-pigs. He observed a complete destruc- 
tion of the microbe by the peritoneal fluid — an agglutination into 

17 



258 



A TEXT-BOOK OF PATHOLOGY 



masses and a gradual degeneration. There were few, if any, leukocytes 
present, and he, therefore, claimed that such destruction was entirely ex- 
tracellular and humoral in character. This property of destroying or 
dissolving bacteria has been termed the "lytic" action of serum. How- 
ever, if a preliminary injection of some substance that determines a local 
leukocytosis is made, there may occur, instead of the reaction of Pfeiffer, 
a true phagocytosis. Metschnikoff interprets Pfeiffer's phenomenon 
as the result of a dissolution of the leukocytes by bacterial action, and 
solution in the peritoneal fluid of the bacteriolytic substances. 

While an important part must be admitted to phagocytes in the 
ultimate destruction of bacteria, bacteriolysis may occur independently 
of phagocytes. 

The bacteriolytic substance has been found to operate outside of 
the body, though not so actively as in the peritoneal cavity. When 
it has been partly destroyed by long standing or heat, the addition 
of a small quantity of normal serum from the same animal species 
restores the bacteriolytic power. (These phenomena will be again 
referred to in the discussion of Ehrlich's Theory.) The sources of the 
bacteriolytic substances are the spleen, bone-marrow, lymphatic glands, 
thymus gland, and doubtless other organs as well. It is probable that 
the source differs in different infections. 

Bacteriolysins differ from Buchner's alexin in being specific in action, 
and, therefore, operative only in the case of bacteria to which the 
animal has been immunized. The bacteriolysins are closely related to, 
if not identical with, hemolysins, substances occurring in the plasma 
under certain conditions and capable of destroying red blood-corpuscles. 
(See Ehrlich's Theory.) 

Opsonins. — Wright and others have demonstrated in the serum 
of animals certain thermolabile bodies which, acting upon bacteria, 
sensitize them for phagocytosis. These substances, which have been 
termed opsonins, are analogous in constitution to toxins in having a 
haptophore group by which they attach themselves to the bacteria, and 
an opsoniferous group, which resembles the complements, and, acting 
like a ferment, completes the sensitization of the bacterium. 

The natural serum opsonin is thermolabile, but that arising in im- 
mune animals is decidedly more resistant to heat. It is believed by 
many that native opsonin is akin to complement or alexin, while that 
appearing after active immunization is in the nature of a specific anti- 
body and, therefore, a new development. Such antibodies are certainly 
specific for the type of organism, if not individually specific. There has 
been a tendency to minimize the effect of the leukocytes by those 
engaged in opsonin work. The phagocytes are not inactive or neutral, 
leaving all the work to the serum opsonin. Whether or not we accept 
the theory that all such free serum bodies come from the leukocytes, 
these cells are undoubtedly responsible for certain increase or decrease 
of phagocytic power, as we have found in certain subacute infections 
(see p. 254). Leukocytes and their extracts have a slight bactericidal 
effect in vitro, as shown by Petterson. This may have some effect in vivo, 



BACTERIA, THEIR NATURE AND ACTION 



259 



but such an action is not considerable. The substances extracted from 
leukocytes are called "endolysins" by Petterson. 

The knowledge of opsonins and phagocytosis has led to the modern 
uses of dead bacteria or their products for increasing immunity. This 
process has been called vaccination because of its similarity in principle 
to the antismall-pox vaccine. In typhoid vaccination there may be no 
high tide of opsonin or other antibody value maintained for a great 
length of time, but after exposure to typhoid there seems to be a 
prompter and greater response in the vaccinated than in the unvac- 
cinated person. 

Bacterial Agglutination. — Investigations by Gruber, Durham, Widal, 
and others have shown that the serum of animals or men rendered 
immune (naturally or experimentally) to infection with the bacilli 
of typhoid fever, cholera, the Bacillus coli, etc., causes agglutina- 
tion and flocculent precipitation of the respective bacteria from their 
bouillon cultures. Such reactions may be obtained with dead bacilli 
under certain conditions and even with inert matters held in suspension. 
(For further details see Typhoid Fever.) This phenomenon (reaction 
of Gruber-Widal) has been interpreted as representing the mode of de- 
fence of the body against infection, and the reaction has, therefore, been 
considered as one of immunity. The reaction, however, bears no rela- 
tion to the severity of the infection or the degree of immunity. The 
serum may be highly agglutinative and yet have no immune properties. 
Some have thought that the agglutination is closely associated with 
bacteriolysis, perhaps as a preparatory step, but the two functions are 
certainly distinct. 

Recent experiments seem to show that two substances are con- 
cerned in agglutination — an agglutinable and an agglutinating body. 
The latter appears to be albuminous or related to serum-globulin, as 
it is precipitated with the latter by magnesium sulphate. It is much 
more resistant to heat than alexin. 

Ferment Theory. — A ferment theory has been offered in explanation 
of some of the phenomena of immunity, but it is of only restricted inter- 
est or importance. Certain bacteria, like pyocyaneus, typhoid, and 
cholera bacilli, are capable of elaborating ferment-like bodies that have 
been designated pyocyanase, typhase, and cholerase. These have some 
bacteriolytic power, and natural immunity has been explained by 
assuming the presence in the plasma of such ferments. The action of 
these ferments is not, however, specific, and their relations to other 
bacteriolytic bodies is still obscure. 

Toxin Immunity. — The probable nature of toxins has been dis- 
cussed on page 249. It is found in some cases that an animal is suscep- 
tible to the action of the toxin of a certain bacterium, though refractory 
to the bacterium itself, and the reverse may also occur. It is clear, there- 
fore, that the resistance to bacteria and to toxins are distinct processes, 
though the two are in most instances associated in the same animal. 

Natural Toxin Immunity. — Certain classes of animals exhibit natu- 
ral toxin immunity just as we have seen natural bacterial immunity 



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existing in certain animals. The immunity of the hog to snake 
venom, of the chicken to tetanus toxin, of the rat to diphtheria 
toxin, and other examples might be cited. The explanation of this 
natural immunity is still uncertain. It is supposed that the immunity, 
which is an hereditary one, originally occurred in the ancestors as a 
result of the infection or intoxication in question. They then trans- 
mitted the immunity to their descendants. With the discovery of 
antitoxin (to be described below) it seemed likely that an explanation 
of natural toxin immunity had been discovered, but it was found that, 
in the case of the chicken and rat, not a trace of antitoxin is present 
in the blood, though these animals are highly immune to the toxins 
of tetanus and diphtheria respectively. It was also found that in these 
animals the introduction of the toxins, while producing no symptoms, 
rendered the serum highly toxic, and that, transferred to other animals, 
this serum produced the symptoms of the diseases named. The toxin 
evidently circulates in an unaltered state at least for some time, and the 
immunity is not due either to destruction of the toxin or to its rapid 
elimination; and as antitoxin is absent, it seems likely that the im- 
munity rests upon an unreceptive quality in the cells of the body. 
Recent experiments have made it clear that toxins attach themselves 
closely to certain cells, as, for example, the nerve-cells in the case of 
tetanus; and it may easily be conceived that if these cells are not recep- 
tive, the toxin might circulate harmlessly in the serum. Experimental 
proof of this view will be cited later. 

The term antitoxin is applied to a substance or substances in the 
serum of an animal that protect against the toxin of a specific disease. 

Acquired Toxin Immunity. — This condition was first explained by 
Behring in a manner similar to the explanation at that time offered 
for natural toxin immunity — that is, he taught that the tissues of 
the body become accustomed to the toxin, a sort of Mithridatization. 
Later he recognized that the resistance is due to the presence of an 
antitoxin. This at first was regarded by many as an altered form 
of toxin, and among other experiments offered to prove this view was 
that of generating antitoxin in vitro by the action of either a continuous 
electrical current or a rapidly interrupted direct current. It is very 
likely, however, that the supposed antitoxin in this case was simply a 
toxin of lower virulence, and that its seemingly antitoxic character was 
really due to its capacity for developing immunity when injected into 
animals. 

Behring first produced antitoxin of diphtheria, but since his investi- 
gations antitoxins of tetanus, snake-venom, and of various infectious 
poisons, mainly of laboratory interest, have been produced. The pro- 
duction of antitoxin is accomplished by treating an animal at first with 
small, and later with larger, doses of the toxin until the antitoxic 
quality is developed. As a matter of practical procedure in some cases 
(e. <?., diphtheria) cultures that have been sterilized by heat or cultures 
containing bacteria of low virulence are frequently used in the early 
injections, and later, when a certain degree of immunity has been pro- 



BACTERIA, THEIR NATURE AND ACTION 



261 



duced, the animal is inoculated with virulent cultures until the antitoxin 
reaches a maximum. When toxin of sufficient strength can be obtained, 
the antitoxin can be most surely prepared by using the toxin alone. 

Occasionally antitoxin is found in the normal animal or in man 
without previous occurrence of the infection under consideration; thus, 
in a notable proportion of normal horses, diphtheria antitoxin is found 
in the blood, and the same is true of children and of adult human beings. 
In these latter, of course, the possibility of a slight attack of the disease 
occurring in early life and having been overlooked must be considered. 
In animals, such as horses, in which the disease does not occur spon- 
taneously, this explanation does not hold. In the light of recent knowl- 
edge it seems probable that antitoxin may be produced by the cells 
under stimulation other than that of the specific toxin, and while anti- 
toxins are specific to a very large degree, so that that of diphtheria pro- 
tects only against the diphtheria poison and that of tetanus only against 
the tetanus poison, this specificity is not absolute. It is known that 
diphtheria toxin protects against abrin-poisoning, and the antitoxin of 
abrin protects against abrin- and ricin-poisoning, while the tetanus 
antitoxin is partially preventive against snake-venom. In other words, 
the blood has some natural antitoxic power which is increased as a 
non-specific body at the same time that specific antitoxins are being 
formed. Moreover, there are certain common constituents in various 
antitoxins that may possess a generic antitoxic power. 

Several years ago Theobald Smith showed that a nearly neutralized 
mixture of toxin and antitoxin produced a more lasting immunity to 
toxin than simple toxin. This has lately been put to practical use by 
Behring and his students. The loose chemical union of the two, 
formed in vitro, is broken up in part by the body, which then proceeds 
to form its own antitoxin. A too rapid effect of freed toxin is held in 
check by the accompanying antitoxin. 

Action of Antitoxin. — It was first thought by Behring that the toxin 
and antitoxin enter into a chemical combination which completely de- 
stroys the identity of the two substances. This was disproved by the 
discovery that a mixture of snake toxin and its antitoxin, which ordi- 
narily has no effect when injected into an animal, becomes highly toxic 
when heated to 70° C. (158° F.). It is known that the antitoxin is de- 
stroyed at this temperature, while the toxin is not. It is very probable 
that the toxin and antitoxin enter into a form of loose chemical com- 
bination without losing their identity, just as hydrochloric acid enters 
into loose combination with albumin in gastric digestion. 

The Chemical Nature of Antitoxin. — But little is known regarding the 
antitoxins excepting that they are relatively resistant to heat and other 
external agencies. Thus, the tetanus antitoxin bears a temperature of 
up to 70° C. (158° F.), as well as the action of sunlight, and even 
putrefaction, without being destroyed. It seems likely that the anti- 
toxins are albuminous bodies or that they are closely associated with 
such bodies. 

Transmission of Antitoxin. — The hereditary transmission of anti- 



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A TEXT-BOOK OF PATHOLOGY 



toxin has been studied, and it has been found that transmission takes 
place from the mother to the offspring through the fetal circulation or, 
after birth, through milk. There is no transmission from an immune 
male parent to the offspring. In experimental work the transmission of 
immune substance could not be traced as far as the second generation. 

Elimination. — Antitoxin is probably eliminated through all the 
secretory organs. It has been found in the urine and to a large extent 
in the milk. Brieger and Ehrlich obtained a quite concentrated form 
of antitoxin by precipitation of the globulin by ammonium sulphate 
and purification by dialysis. As in the case of toxins, the whole of 
the antitoxin seems to be carried down by the precipitated globulin. 

All the phenomena of immunity have been explained by Ehrlich 
in a very comprehensive theory called the side-chain theory. The 
applications of this to toxin immunity will be first considered for the 
sake of simplicity. 

Ehrlich's Side-chain Theory. — Toxin Immunity. — This theory 
explains the facts regarding the action of toxins and the formation of 
antitoxins better than any that has been suggested. It is based upon 
the hypothesis that bacterial toxins, like assimilated foodstuffs, enter 
into chemical combination with the cells of the body. In this respect 
toxins differ from ordinary poisons which do not enter into such com- 
bination, and this may explain the failure of all experiments at produc- 
tion of antitoxins for such poisons. Some non-bacterial poisons, such 
as snake-venom, abrin, ricin, etc., resemble toxins in combining with the 
cells, and it is notable that in the case of these poisons antitoxins have 
been produced. The combination between a toxin and a cell is effected 
by atom groups or radicals (to borrow terms from organic chemistry), 
the group of the cell entering into combination with the group of the 
toxin. It is assumed that the body-cell is like a complex chemical sub- 
stance with unsatisfied bonds, to which is added the power to combine 
with substances having affinity for it through these bonds, and to cast 
them off after this new combination is effected. These groups which 
effect the junction of the cell and the toxin are termed haptophore 
groups. In addition to its haptophore group, the toxin molecule con- 
tains a toxophore group which carries the toxic capacities, but the toxo- 
phore group cannot operate upon a cell until the toxin has been anchored 
to the cell by the junction of the haptophore groups (Fig. 96). When a 
toxin is introduced into the body, it finds cells with haptophore groups 
having affinity for its own haptophore group. These haptophore 
groups of the cells, from their receptive function, are called receptors, 
and they are specific in so far as the receptors of certain cells will 
combine with the haptophore groups for which they have affinity 
and with no others. In this way it may happen that a highly toxic 
body may circulate harmlessly in the body, as there are no receptors 
for which it has affinity. (This matter was referred to in the paragraph 
on Natural Toxin Immunity.) 

When the receptors of the cells are utilized by combination with the 
haptophores of the toxin they may be regarded as neutralized or practi- 



BACTERIA, THEIR NATURE AND ACTION 



263 



cally destroyed, and the cell has suffered a "defect" which must be re- 
placed by regenerative processes. This usually follows promptly, accord- 
ing to the well-known theory of Weigert that destruction is followed by 
regeneration. In accordance with the same theory this regeneration 
often more than replaces the loss, so that in the case under discussion 
there is an overproduction of receptors in the cell, and some of these are 
extruded from the cell into the blood-plasma. The actual extrusion or 
separation of the haptophore groups requires the stimulus of the toxo- 
phore group. The separated haptophore groups how free in the blood- 
plasma constitute the antitoxin, since they are now free and able to com- 
bine with the toxins before these can reach cells susceptible to the action 
of the toxophore group. The toxin thus combined with a liberated recep- 




I H m 



Fig. 96. — Receptors of three orders (Ehrlich) . 
Ehrlieh has described receptors of three orders: 1, The receptor of the first order is a 
single combining group without any other function. On this account Ehrlich speaks of 
it as a uniceptor. In Fig. 96, /, such receptors are shown at a. On the right hand, the 
receptor has become united with a toxin molecule, 6. The latter shows its haptophore 
group at c, and its toxophore group at d. It is the receptor of the first order that con- 
stitutes antitoxin when liberated from the parent cell. 2. Receptors of the second order 
(Fig. 96, II, c) have a haptophore group, e, and a zymophore group, d. The latter is so 
named because of its ferment-like capacities. On the right hand is seen a molecule of 
nutrient matter, /, combined with the haptophore group of the receptor, in such position 
that the zymophore group can act upon it. Having but one haptophore group, like the 
receptors of the first order, those of the second order also are included under the term of 
"uniceptors." The phenomena of agglutination and precipitation are probably occasioned 
by this second order of receptors.. 3. Receptors of the third order (Fig. 96, III, i) carry 
two haptophore groups, e and g. One of these combines with a molecule or cell, /, for 
which the receptor has affinity, and the other combines with the haptophore group of the 
complement, k, which, when so combined, can act upon the molecule anchored to the 
other haptophore group. The complement has two groups — one, its haptophore, h, and the 
other, its zymotoxic group, z. 

tor (antitoxin) is incapable of harm, as its own haptophore group is 
promptly joined to the antitoxin and cannot, therefore, become an- 
chored to a vulnerable cell, which is the prerequisite for the operation 
of the toxophore group upon a cell. After antitoxin formation has 
begun, it may continue for some time, causing successive discharges 
of the antitoxic material into the blood-stream. This is shown by the 
continued presence of antitoxin in animals that have been bled so 
abundantly that practically all the original blood must have been with- 
drawn. 

All the steps in this theory have been practically demonstrated. 
In the first place, it has been shown that the toxin enters into firm 
combination with the cell by mixing tetanus toxin and emulsions of 



264 



A TEXT-BOOK OF PATHOLOGY 



normal brain tissue. Under these circumstances a certain proportion, 
or all, of the toxin unites with the nerve-cells, and the mixture is found 
to be harmless when injected into animals. In the second place, it has 
been shown that the receptor formation results from the combination 
of the haptophore groups of the toxin and of the cell, and is independent 
of the toxophore group. This was demonstrated by producing increased 
susceptibility to the action of toxin in animals inoculated with toxoid 
(a body derived from toxin, but having no toxic qualities). The toxoid 
has the same combining capacity for receptors of the cells as has the 
toxin, but it simply lacks the toxophore groups, which somehow have 
disappeared or become altered. In the experiment just quoted there 
was no trace of antitoxin in the blood; hence the toxoid was capable of 
causing increased production of receptors on the cells, but not free in the 
blood as antitoxin. Other experiments show that the stimulus of the 
toxophore group is necessary to cause the separation of new-formed 




/ ~ H 



Fig. 97. — /. Scheme showing cell with receptors (a). One receptor has been occupied 
by a toxin molecule (6). There has resulted an overproduction of receptors, and two of 
these (a') have become separated from the cell. 

II. Scheme showing toxin molecules (6) attached to free receptors (a') in the blood. 
The toxin is thus prevented from attaching itself to the receptors (a) of the cell, and the 
toxophore group (d) is harmless. 

receptors from the cell. In the third place, it has been shown that the 
antitoxin formation takes place in the fixed tissue cells, where the toxin 
finds suitable receptors, and not in the circulating blood itself, since 
antitoxin could be extracted with salt solutions from the blood-making 
organs of animals that had been treated with toxin, but had not yet any 
antitoxin in the blood. Of course, the period of time during which such 
an experiment could succeed must be a very brief one, but it has been 
accomplished. 

Numerous experiments have shown that the antitoxin is not altered 
toxin, but a new production, as stated in this theory. The large amount 
of antitoxin produced by a small amount of toxin alone would suffice 
to disprove the theory of transformation. 

Haptophore groups or receptors still in connection with the parent 
cell are not to be regarded as antitoxin; rather the contrary, for they 
serve to anchor the toxin to the cell where the toxophore group is in 



BACTERIA, THEIR NATURE AND ACTION 



265 



position to injure the cell (Fig. 97). The experiment quoted above 
showed this, for the animal treated with toxoid developed increased 
vulnerability to toxin (because of the increased number of receptors) 
and had no trace of antitoxin in its blood. It is only haptophore groups 
that are free in the circulation, and therefore capable of fixing toxin and 
keeping it away from the cells that constitute antitoxin. 

This antitoxin production Ehrlich ascribes to his uniceptors or 
receptors of the first order. It is the simple union of toxin haptophores 
and fixed or free cell receptors. 

Bacterial Immunity. — (a) Bacterial immunity as applied to agglu- 
tination and precipitation is next in order. These processes are ex- 
plained by Ehrlich's receptor of the second order. This assumes that the 
cell receptor has two parts, one to combine with the haptophore of the 
bacterium or other body, the other a zymophoric part, to act upon the 
toxophoric part of the bacterium (see Fig. 96). 

These processes — agglutination and precipitation — are not actively 
concerned in the phenomena of immunity, but may be referred to in this 
place on account of their illustrating the applications of the side-chain 
theory. 

Agglutination. — Bacterial agglutination (Pfeiffer-Gruber-Durham 
phenomenon) is explained by Ehrlich's theory somewhat in the same 
way as bacteriolysis and hemolysis. In the case of agglutination, how- 
ever, there is but one agent — a liberated amboceptor having a hapto- 
phore group, which attaches itself to the bacterium, and a zymophore 
group, which plays a part similar to that of the complement in bac- 
teriolysis (see Fig. 96, II, d). It differs from the complement, however, in 
that the zymophore group is an integral part of the amboceptor, and not 
a separate body, which attaches itself to the latter. A serum which has 
the property of agglutinating the bacteria of a certain disease (as e. g., 
typhoid fever) contains liberated amboceptors that were set free by 
the cells of the body and that have the property of attaching them- 
selves to the specific bacteria concerned in that disease. When so 
attached, their ferment-like group or zymophore group, which is the 
active agent, produces agglutination. The zymophore of the antibody 
is the agglutinating substance or agglutinin, while the corresponding 
fraction of the bacterium is the agglutinable body. This was mentioned 
on p. 259. (See also Typhoid Bacillus.) Agglutinins are also found in 
normal blood, although in but small quantity. They are thermostabile, 
and resist drying of the serym. 

Precipitin. — The phenomena of precipitation of various substances 
that have been introduced into an animal organism by the action of 
serum derived from the blood of such animals have been ascribed to 
specific "precipitins." Thus, when the blood of human beings is repeat- 
edly introduced into the peritoneal cavity of rabbits, the rabbit-serum 
acquires the property of precipitating human blood. When the blood 
of several animals in succession is introduced into an animal of a differ- 
ent species from each of these, it is found that the precipitation is a 
specific process, since the specific power to precipitate the blood of each 



266 



A TEXT-BOOK OF PATHOLOGY 



of the species employed can be successively demonstrated. When 
albuminous liquids or such a complex mixture as milk is introduced 
into animals, the blood-serum of the animals acquires the property of 
precipitating the albumin used or the milk (casein). This and other 
experiments show the wide range of applicability of the principle of 
precipitation. Ehrlich explains the process of precipitation in the same 
way as that of agglutination, by the assumption that amboceptors 
carrying haptophore groups with an affinity for the precipitable body 
are set free in the serum, and that associated as an integral part of these 
amboceptors are zymophore groups capable of producing the phenomenon 
of precipitation or agglutination. The zymophore groups are destruct- 
ible by heat, though the degree of heat is much higher than that re- 
quired to destroy the complements concerned in bacterial destruction 
and hemolysis. 

(6) Bacterial Immunity as Applied to Bacteriolysis and Cytolysis. — 
The application of Ehrlich's theory to the phenomena of bacterial 
immunity is quite as satisfactory as it is to the formation of antitoxins. 
When a bacterium is introduced into the body, the problem of the 
defence of the organism against the invading bacterium is much more 
complicated than that of the defence against a toxin, because the bac- 
terium contains a variety of substances, such as its protein and various 
ferments, and may elaborate specific toxins in the culture-medium. 
In consequence, the defence of the animal organism against the bac- 
terium is a complicated one, involving formation of antitoxin and 
other antagonistic bodies, including those which attack the bacterium 
itself in contradistinction to the products of the bacterium. The 
defense against the bacterium is the process that has been referred 
to previously in describing Pfeiffer's phenomena of bacteriolysis. 
This process, according to Ehrlich's investigations, is practically identi- 
cal with that of hemolysis, or destruction of red corpuscles, which occurs 
when the blood of one animal is injected into another, or when certain 
hemolytic agents, like snake-venom, are introduced into the blood. 
As the study of hemolysis is practically much easier than that of 
bacteriolysis, the theory was elaborated on the bases of experiments in 
hemolysis, and two distinct substances or bodies are involved in the 
process. One of these Ehrlich formerly designated as the intermediary 
body in the case of hemolysis, or the immune body in the case of bacterial 
immunity; the second is a complementary body, and is designated the 
complement. The intermediary body, or immune body, is a product of 
cell activity under the influence of infectious, toxic, or other agencies, 
which is set free in the same manner as the haptophore group or re- 
ceptor in the case of antitoxin formation. It has two haptophore 
groups — one having affinity for the complement, and therefore desig- 
nated complementophilic; and the other having affinity for the bacterium, 
red corpuscle, or other cell, and therefore designated cytophilic. On 
account of this possession of two haptophore groups Ehrlich later desig- 
nated the intermediary body by the term amboceptor. This is Ehrlich's 
receptor of the third order. It is a stable substance, not influenced by 



BACTERIA, THEIR NATURE AND ACTION 



267 



moderate heat. The complement, on the other hand, is a ferment-like 
body, and is a constituent of normal blood-plasma. Its ferment-like 
character is evidenced by its ready destructibility by heat (55° or 56° C; 
(131° or 132° F.). The origin of complement has been variously ascribed 
to leukocytes, lymph-glands, and liver. Without the complement the 
amboceptor is ineffective, and without the amboceptor the comple- 
ment cannot affect the cells (bacteria, red blood-corpuscles, etc.). The 
cytophilic group of an amboceptor is more or less specific, so that, unless 
the receptors (haptophore groups) of the bacteria, red corpuscles, etc., 
are homologous with the cytophilic haptophore of the amboceptor, 
combination will not occur — in other words, the amboceptors are more 
or less specific and must be homologous with the receptive haptophores 
or receptors of the cells. There must, then, be a great many varieties 
of receptors — perhaps hundreds or thousands — in order to fix the equally 
numerous varieties of amboceptors, and the same is perhaps true of 
the complement. Various substances doubtless act as complements. 
Thus, in experiments on snake-venom, Kyes found that lecithin is the 
complement. 

The bacteriolysin of Buchner, called by him alexin, is, according to 
recent views, a compound substance, one part being the amboceptor, the 
other the complement. 

Explanation of Pfeiffer's Phenomenon. — The phenomenon of Pfeif- 
fer's bacteriolysis may be explained in the following manner: When a 
bacterium, with a quantity of immune serum, is introduced into the 
peritoneal cavity of a non-immunized animal, amboceptors derived from 
the immune serum attach themselves to it. The complement present 
in the peritoneal fluid then becomes anchored to the complementophilic 
haptophore group of the amboceptor, and in this position is able to bring 
about the solution of the bacterium and its destruction. The phe- 
nomena of hemolysis may be explained in the same way : the amboceptor 
first attaches itself to the red corpuscle, and the complement (hemolysin) 
in turn attaches itself to the amboceptor. 

The necessity for two bodies in the production of these phenomena 
has been thoroughly demonstrated. It is known that serum capable of 
producing Pfeiffer's phenomena in vitro loses this power when subjected 
for a certain length of time to heat or sunlight. A prompt restoration 
of the power follows the addition of small quantities of normal (unheated) 
serum of the same animal species. This proves that a ferment-like body 
(destroyed by heat) is a necessary factor, and that this ferment is 
present in the normal serum of the animal. The importance of the 
complement has been further demonstrated by the formation of anti- 
complements, which are capable of combining with it and thus stopping 
its action. When the anticomplement is withdrawn, the complement 
is again capable of operating. In a similar manner anti-amboceptors 
have been produced, and have sometimes been found in the blood of 
normal animals. 

The following scheme represents graphically the relations of the 
amboceptor and complement to the cell and the possibilities of the 



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A TEXT-BOOK OF PATHOLOGY 



various antibodies, such as the anticomplement and anti-amboceptor 
(Fig. 98). 

Cytolysin. — Injections of emulsions of various cells into animals 
have been found to generate destructive substances in the serum of the 
experimental animals. These destructive bodies are specific for the cells 
used in the experiment. Thus, spermatolysin, epitheliolysin, and hep- 
atolysin are substances which will cause destruction of spermatozoa, 




Fig. 98. — I. Diagram representing the amboceptor and complement free and attached 
to the cell by means of the appropriate receptor. II and III. Scheme showing (1) pos- 
sible antibodies; (2) anti-amboceptor; (3) anticomplement; both of these have been 
demonstrated as possible antibodies, a, Cytophilic group; b, complementophilic group. 

epithelia, and hepatic cells respectively. The phenomena involved 
in such cytolysis are closely allied with those of bacteriolysis and 
hemolysis.. 

The following tables (modified from Muller) will show in a con- 
densed form the varieties of immunity detailed in the foregoing para- 
graphs : 

Antitoxic Immunity 

I. Cellular. 

A. Lack of appropriate receptors. 

(a) Congenital. 

(b) Acquired (loss of the receptors). 

B. Lack of susceptibility to the toxophore group of the toxin. 

(a) Congenital. 

(b) Acquired (?). 

C. Attachment of the toxin to insusceptible tissues. 

(a) Congenital. 

(6) Acquired (development of new receptors in insusceptible tissues). 

II. Hematogenic. 

A. Active. 

(a) Manifest form (abundance of antitoxin in the blood). 

(b) Latent form (no antitoxin present, but capacity for making it 

quickly and abundantly). 

B. Passive. 

Antitoxin is introduced : 

(a) Through the placenta to the fetus. 
(6) Through milk to the nursling, 
(c) By direct injection. 



BACTERIA, THEIR NATURE AND ACTION 



269 



Antibacterial Im m un itt/ 

I. Natural (congenital). 

(a) The animal organism is an unsuitable medium for the growth of the 

bacterium. 

(b) The organisms are destroyed at the point of infection by amboceptors 

and complements (bacteriolysis). 

(c) Amboceptors present, but no complements. 

The latter are supplied by — 

1. Increased supply of tissue fluids. 

2. Advent of wandering cells. 

(d) Complement present, but no amboceptors. 

The latter are supplied — 

1. Locally. 

2. By the lymphoid blood-making organs. 

(e) Phagocytosis and intraphagocytic bacteriolysis. 

II. Artificially increased, but not specific (pseudo-immunity). Injection of 

irritating substances which cause local accumulation of phagocytes and 
bacteriolysins. 

III. Naturally acquired specific immunity. 

IV. Artificially acquired specific immunity. 

(a) Active immunity. 

1. Abundant presence of specific amboceptors in the blood and tissue 

fluids. 

2. No preformed amboceptors, but increased capacity to manufacture 

such, by prophylactic injection. 

(b) Passive immunity. 

Specific amboceptors in the blood (derived from another animal) . 

Complement Deviation and Fixation. — When complement is bound 
in such manner that it cannot enter into combination with antigen and 
amboceptor in bacteriolysis or eytolysis, it is said to be "deviated" or 
"fixed." The terms, however, are used for slightly different conditions. 
If more antibodies be employed in tests or injections than the antigen 
can use, the excess combines with complement and prevents it from 
acting with the antibodies bound to the antigen. This is complement 
deviation, and of slight moment here, except to be contrasted with 
complement fixation as a diagnostic procedure. If the serum of rabbits 
immunized against sheep erythrocytes be mixed with sheep red cells in 
the presence of complement derived from normal guinea-pig serum, 
hemolysis results. When, however, complement is absorbed, as now 
to be shown, hemolysis will not occur. A mixture of the serum of a 
person suffering from a micro-organismal disease, an emulsion of the 
causative microbe, and guinea-pig serum containing complement results 
in the solution of the germs, i. e., bacteriolysis, because the three factors 
— antigen, amboceptor, and complement — are present and are bound 
together. If, now, we were to add to this same mixture the antisheep 
cells rabbit serum and the sheep cells, no solution of the hemoglobin 
would result because the complement has been fixed by the first combina- 
tion. This is the principle of the Wassermann reaction in syphilis. It 
can be and is used chiefly for determination of the presence of antibody 
in the blood of infected persons. The application to syphilis will be 
discussed later. We refer to works on immunology for deeper con- 
sideration. 



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Anaphylaxis or hypersusceptibility is a condition of increased or 
altered susceptibility of the animal organism to foreign protein. In a 
sense, then, it is a condition opposed to immunity, although in some 
cases it may act to protect the body against infection. The term 
allergie has been suggested by von Pirquet to express the altered and 
usually increased property of the body to react to foreign protein. 

Hypersusceptibility may be natural or acquired. The former is 
exemplified by the susceptibility of certain persons to pollen in rose-cold 
and hay-fever, or to fish and oysters which is shown by skin eruptions. 
Acquired hypersusceptibility is expressed when the body, once having 
received a foreign protein, is exposed to it a second time. For example, 
if a guinea-pig receive a small dose of horse serum, no symptoms will 
arise, but when a somewhat larger second dose is given, after an incuba- 
tion period of eight to ten days, it will almost immediately become 
depressed and nervous, scratch its nose, develop violent dyspnea, and 
die ; the fatal outcome occurs usually within an hour, but may appear in 
a few minutes. Upon postmortem examination there will be found spas- 
tic dilatation of the pulmonary alveoli of local and central origin, 
hemorrhage into and ulceration of the gastric mucosa, and scattered 
petechial hemorrhages. The death is due to respiratory failure, as the 
heart continues to beat after respiration has ceased. This sudden and 
violent reaction is called "anaphylactic shock," a condition most clearly 
expressed by the guinea-pig, which animal seems to exhibit the most 
pronounced reactions in allergie tests. Any animal, however, is capable 
of anaphylactic phenomena, and the symptoms, signs, and pathology are 
similar in all. The reactions differ in degree, of course, depending upon 
the amount and nature of protein injected, the incubation period, and 
the receptivity of the animal. If the amount of serum injected the 
second time into the guinea-pig be too small, or if introduced so that the 
absorption is quite slow, symptoms will be delayed, milder, and may not 
proceed beyond nervousness and scratching. If the dose be given into 
the skin instead of under it or into the circulation, only a local reaction of 
redness and edema may be occasioned. The injection first given is called 
the sensitizing dose; the second, the intoxicating dose. 

In the discussion of infection and allergie given below it will be seen 
that previous exposure to a protein (bacterial) acts as the first dose, while 
the place of the intoxicating dose is taken by the protein (bacteria) from 
which the infection immediately arises. 

Hypersusceptibility is specific, that is, an animal will be intoxicated 
only by the protein with which it has been sensitized. Guinea-pigs 
may be sensitized to several proteins and react specifically to each. 
The allergic state is transmissible to young from the mother only; if 
the father only be sensitized the offspring does not inherit the condition. 
During the anaphylactic reaction there will be found leukopenia with 
eosinophilia, lengthening of the blood coagulation time, and a fall in 
blood-pressure. 

The allergic state is sometimes seen in human beings after the injec- 
tion of antisera, notably diphtheria antitoxin. The reaction takes the 



BACTERIA, THEIR NATURE AND ACTION 



271 



form of "serum sickness" or anaphylactic shock. Serum sickness oc- 
curs after an incubation period of a week to ten days, and is character- 
ized by nervous depression, skin irritation, urticarial eruptions, fever, 
and malaise; occasionally the condition may be quite severe, appearing 
like an acute general infection. Anaphylactic shock in human beings 
after serum injections is similar to that outlined for guinea-pigs, and 
death may ensue in a few minutes. The vast majority of cases in which 
this acute reaction has been observed have suffered from asthma. In 
this connection an explanation has been sought in the fact that the 
anaphylactic reaction sets up spasm in involuntary muscle; that the 
muscles of the bronchi are contracted and shut off the alveoli. 

Allergie also explains the responses obtained when the skin of a person 
suffering from an infectious disease is inoculated with some of the virus 
of that disease. This phenomenon is exemplified by the skin reaction 
against tuberculin exhibited by the tuberculous, and the luetin reaction 
in syphilitics. It is a local manifestation of general anaphylaxis. 

There is a general tendency now to use this anaphylaxis, or the allergic 
state, to explain the contraction of infectious disease. It is assumed that 
when a person contracts such a disease he has been susceptible to the 
organism as an individual peculiarity, or has been prepared, sensitized, 
in some way. 

One explanation of this phenomenon asserts that the body is unpre- 
pared for protein introduced at other places than the alimentary tract, 
and must prepare a ferment against it. This it does after the first dose, 
but in accord with Weigert's overproduction theory, it produces a 
superabundance of this ferment, which, when acting upon the second 
dose, breaks it up so quickly that various digestion products are thrown 
on the organs suddenly and poison them. Another theory assumes that 
toxic protein circulates in the blood after the first dose; the body cells 
are poisoned by it, but gain an affinity for it, so that they attract it in 
large quantity after the second injection, being then fatally injured. 
Friedberger views the anaphylactic reaction as the effect of toxic pro- 
teins upon cells through their sessile receptors, thus permitting a direct 
injury to the cell protoplasm. It is not until several injections have been 
given that receptors are freed and combine with toxic substances, apart 
from cells. This is in accord with Ehrlich's theory that cells are vulner- 
able in proportion to the number of their sessile receptors. 

Friedberger has used the "principle to develop his anaphylotoxin 
theory of infection. He assumes that an organism circulating in the 
body combines with the antibodies it has stimulated. This combina- 
tion is then rendered toxic when acted upon by complement. Jobling 
goes further than this, asserting that bacteria absorb the unsaturated 
fatty acids of the blood, which hold in check the tryptic power of the 
serum, permitting the serum to break up bacterial and natural proteins 
and allowing escape of their toxic elements. 

Vaughan believes that the invasion of the body by bacteria stimu- 
lates a ferment which, acting upon the organisms, frees their toxic pro- 
tein. The ferment is specific for the infecting germ and will react 



272 



A TEXT-BOOK OF PATHOLOGY 



quickly when this enters the body the second time. The toxic fraction 
of all bacteria is the same. He explains infection and allergie on this 
basis. The specific antibodies are stimulated by the specific protein, 
so that typhoid bacilli have their own, pneumococci theirs, etc. It 
certainly seems that the anaphylactic state is due to degradation 
products of proteins and that the substances giving rise to it are complex 
proteins. The body fluids seem to react to the parenteral introduction 
of proteins by the elaboration of ferments having the power to break 
down these substances into simpler combinations like the amino-acids. 
Abderhalden has shown that in the serum of pregnant women there are 
ferments capable of digesting placental tissue. It may be that all im- 
munity phenomena are protein reactions on the part of the body. 

Chemistry of Antigens and Immune Bodies. — The exact composi- 
tion of the various elements that have been brought to light by immunity 
researches is not known. Some observers maintain that only proteins 
can give rise to the immunity phenomena, but others believe that some 
lipoids and glucosids can act as antigens. No substances simpler in 
composition than peptones seem able to act as antigens. Judging from 
the work of Vaughan and Abderhalden upon bacterial and other pro- 
tein intoxication, the defenses of the body seem all to be directed against 
foreign protein. These proteins are specific, in that protection or sus- 
ceptibility toward one will not protect or dispose toward another. 
The various substances in the serum involved in immunity or allergie 
are precipitated with protein fractions, seem inseparable from them, 
and cannot be obtained in a pure state. The method of action, be it 
chemical, mechanical, or electrolytic, is not known. It might be well to 
emphasize here that in speaking of this parenteral introduction of pro- 
tein a substance foreign to the tissue is implied. 

Meiostagmin Reaction. — This is a test for showing the reduction of 
surface tension by the combination of antigen and specific antibody. 
For this purpose Traube's stalagmometer, an instrument to determine 
the number of drops in a given bulk, is used. If homologous antibody 
and antigen are mixed and incubated at body temperature for two hours, 
there will be found an increase of drops over the number determined 
before incubation. Some have used this test as an argument for the 
physicochemical explanation of immune reactions. Its significance is 
not yet fully understood. 



CHAPTER IX 



DISEASES DUE TO BACTERIA 

The bacterial diseases form a large and increasing group. In 
some cases it has been shown by the positive application of Koch's 
rules (see p. 37) that the suspected micro-organisms are the actual 
causes of the diseases under consideration; in more numerous instances 
all of the rules cannot be applied, but other considerations go far toward 
establishing the specific nature of the suspected bacteria; in still other 
cases the evidence warrants a strong suspicion of the pathogenicity of 
bacteria found in connection with certain diseases, but there is nothing 
approaching actual demonstration. 

Diseases Due to Cocci 

suppurative diseases 

Definition. — Under this heading we include for the present various 
forms of suppurative inflammation, such as furunculosis, abscess 
formation, and allied diseases, like osteomyelitis, endocarditis, cellulitis, 
etc. 

Etiology. — Numerous organisms have been found to have the power 
of producing suppuration (pyogenic organisms). Among these the 
staphylococcus group is most important. The Streptococcus pyogenes 
seu erysipelatis is also of great significance; less frequently the Diplo- 
coccus pneumoniae, the pneumobacillus of Friedlander, the Bacillus 
pyocyaneus, the typhoid bacillus, the Bacillus coli communis or the 
Bacillus pyogenes f&tidus, the gonococcus, and others. Some cases of 
suppurative disease are due to a single organism; in many there is 
double or multiple infection. 

1. The Staphylococcus Group. — Among these have been described 
three important forms: the Staphylococcus pyogenes aureus, albus, and 
citreus. 

The Staphylococcus pyogenes aureus is a minute, rounded body 
about 0.5 to 1 ft in diameter, having no motility and not forming 
spores. When found in the tissues the cocci are apt to be associated in 
clusters, whence the term "staphylococcus." Sometimes they are grouped 
in pairs, and may thus present a resemblance to gonococci. The op- 
posed surfaces, however, are flat instead of concave, as is the case with 
the gonococci. The staphylococcus may be stained with ordinary anilin 
solutions and is beautifully demonstrated by Gram's method. Cul- 
tures are easily obtained upon the ordinary media. The most charac- 
teristic growth is that upon agar. Along the line of inoculation a moist 

18 273 



274 



A TEXT-BOOK OF PATHOLOGY 



colony develops, with at first a whitish but soon an orange-yellow color, 
especially under the influence of light. The growth in gelatin causes 
rapid liquefaction and the precipitation of orange-yellow particles. 
The growth is best obtained at oven-temperatures (25° to 35° C; 
77°-95° F.), but may be secured at lower degrees. 

Distribution. — The Staphylococcus aureus is frequently found upon 
the skin or in the various external secretions of healthy individuals. 
It does not seem to flourish anywhere apart from the bodies of men or 
animals, but may remain in an active state in the dust of rooms or 
upon clothing and the like. It has been found in various lesions of the 
body, notably, however, in furuncles, abscesses, and carbuncles, and in 
ulcerative conditions of the exterior or of the mucous membranes. It 
is also frequent in internal suppurative inflammations, such as malig- 
nant endocarditis, osteomyelitis, appendiceal abscesses, etc. In many 
of these lesions other organisms may be associated. 

Pathological Physiology. — Filtrates of the cultures and the bodies of 
the staphylococci (killed by heat) contain highly toxic substances 
capable of producing intense inflammation and suppuration. Certain 
of their products are markedly hemolytic. 

When injected into the subcutaneous tissue the staphylococcus 
produces local effects. The organisms may become liberated, gain 
entrance to the circulation, and produce widespread results; but it does 
not seem to produce extracellular toxins that cause generalized results. 
The effects of the staphylococcus seem to be due rather to a certain 
poisonous body contained in the organism itself. This has been termed 
"bacterial protein," and it has been thought to belong to the group of 
alkaline albuminates. This body by its chemotactic effect causes the 
leukocytic accumulations found in suppurative inflammations. The 
staphylococcus also leads to liquefaction in the tissues, as in gelatin, 
both directly and through the accumulation of bodies derived from 
leukocytes. The defence of the organism against the staphylococcus is 
partly mechanical and partly vital. The leukocytes probably englobe a 
certain number of organisms and cause their destruction, while soluble 
bactericidal bodies seem to be produced in the course of the infection. 

Injection of cocci gives rise to antibodies — agglutinins, opsonins, and 
bacteriolysins. Upon them depends the use of bacterin or vaccination 
treatment. 

Pathogenicity. — When virulent cultures are injected into animals, 
abscesses are produced and a fatal termination may follow. In the latter 
case dissemination through the blood is found, and infarcts of the kid- 
neys, lungs, and other organs caused by bacterial emboli are discovered. 
Multiple abscesses may be seen. The organism readily loses its virulence, 
as in the case of those found upon the skin of healthy persons and in 
other accidental situations. When rubbed in a virulent state into the 
skin of man it produces abscesses or boils. It may remain dormant 
within an enclosed abscess or sequestrum in a bone, or apparently in a 
subacutely inflamed heart valve or muscle, and light up upon some 
secondary infection. Staphylococcus infection tends to remain local, with 



DISEASES DUE TO BACTERIA 



275 



occasional spread to the circulation. Its local lesions are of slower pro- 
gression than those of the streptococcus. Its presence sometimes favors 
the growth of other organisms, notably the influenza bacillus. 

Staphylococcus pyogenes albus (Fig. 99). — This organism is practically 
identical with the last-named in morphology, but in culture produces a 
white instead of a yellow growth. One of its forms has been found as a 
frequent harmless parasite of the skin (Staphylococcus epidermidis albus 
of Welch). It occurs in abscesses and various suppurative diseases, but 
rarely alone. As a rule, it is associated with the golden staphylococcus 
or other organisms. It is distinctly less virulent than the aureus. 

Staphylococcus pyogenes citreus. — This form is the least important 
of the three. It is not so common and, as a rule, less virulent. It differs 
in the brilliant lemon color obtained upon culture in various media. 

2. The Streptococcus pyogenes seu erysipelatis. — Under the name 
streptococcus are included various spherical bacteria which divide only 



in one plane and form chains of varying length. The different forms 
resemble each other so closely that some authors group them all, includ- 
ing the Streptococcus pneumonia', under one general head. The last, 
however, seems sufficiently differentiated to merit separate classifica- 
tion. 

The Streptococcus pyogenes was first studied by Rosenbach in cases 
of suppuration. A similar organism was afterward described as the 
Streptococcus erysipelatis by Fehleisen. It would seem, however, that 
these two organisms are identical. The streptococcus is a small spherical 
organism of variable size (0.5-1 fi), frequently associated in chains of 
from three to twenty or more individuals (Fig. 100). Not rarely it 
occurs in diplococcus forms (as pairs). It is easily stained with ordinary 
anilin solution or by Gram's method. The cocci are not motile. Spore 
formation has not been observed, but occasionally in chains one of the 
individual members is larger than the rest, suggesting arthrospores. 
Upon artificial media scanty but rather characteristic growths are ob- 




Fig. 99. — Staphylococcus pyogenes albus 
(Jakob). 



Fig. 100. — Streptococcus pyogenes 
(Jakob). 



276 



A TEXT-BOOK OF PATHOLOGY 



tained. On the gelatin plate there are formed small, translucent, whitish 
or yellowish colonies of irregular outline. The gelatin is not liquefied. 
Upon agar a very thin, transparent growth forms around the line 
of inoculation. It consists of separate colonies which usually do not 
coalesce. On mixed agar and blood plates the colony of the true 
streptococcus produces a pale gray dot surrounded by an area of hemol- 
ysis. Certain varieties lack this power. In milk the growth is usually 
abundant and attended with lactic acid formation and coagulation of 
the casein. 

In the species Streptococcus pyogenes there are several varieties that 
have been found so frequently under special conditions that they seem 
worthy of separate mention. The principal one is the Streptococcus viri- 
dans, which is common in streptococcal endocarditis. It is not hemolytic 
and grows in green colonies on blood-agar. Streptococcus mucosus is a 
mucus-producing organism found usually in the throat or in enclosed 
abscesses. The streptococci of the feces have minor peculiarities differ- 
ing from the true type. Another variety seems to have a predilection 
for joint cavities (Streptococcus rheumaticus) . 

It has been asserted by Rosenow that the members of the strepto- 
coccus-pneumococcus group are but variants of one species, and he 
claims to have been able to follow a mutation from one to another 
under artificial conditions. Under prolonged artificial cultivations these 
organisms do surely lose some minor characters, but mutation must be 
stationary to be actual. 

The distribution of the streptococcus is much the same as that of 
the staphylococci, though it is less commonly discovered about the 
healthy body. It may, however, be found upon the mucous membranes 
or in the various secretions or excretions of the body. It is probably a 
strict parasite, multiplying only within the living organism. 

In disease it has been found in various forms of suppuration, such 
as phlegmonous forms of inflammation of the subcutaneous or sub- 
mucous tissues, either alone or in association with other organisms. 
It occurs occasionally in focal suppurations, such as abscesses, though 
these are more commonly due to staphylococci alone. The streptococcus 
occurs at times in ulcerative endocarditis, not rarely in infectious endo- 
metritis and in generalized septicopyemia. Streptococcic inflammations 
of the throat are of great interest. They may occur in persons previously 
in good health, or in the course of infectious diseases, like scarlatina, 
measles, or influenza. To the clinician the resulting lesion may be 
indistinguishable from that of diphtheria; bacteriological examination 
alone serves to establish the diagnosis. Deep involvement of the tonsil 
is one infection-atrium for the cocci to enter the blood. Following such 
an entrance we may have serous membrane involvement, particularly in 
the heart valves. The streptococcus is found in all cases of erysipelas 
in the tissues and in the other exudations. 

Pathological Physiology and Pathogenesis. — The streptococcus seems 
to be more active in the production of soluble toxins than staphy- 
lococci. The toxin has been made by inoculating small quantities of 



DISEASES DUE TO BACTERIA 



277 



bouillon with virulent cocci, allowing these to grow for several weeks, 
and then destroying the organisms by heat. The injection of the toxins 
thus produced leads to local and general reaction. While there is a 
certain amount of this extracellular toxin, it seems that most of the 
toxic substances of streptococci are embodied in the micro-organism 
itself. In virulent cultures actively hemolytic bodies are often present, 
and certain streptococcic infections in man are attended with hemor- 
rhages and evidences of hemolysis. 

The principal pathological character of streptococcal infections is their 
spread. Instead of localizing like the staphylococcus, a diffuse spreading 
inflammatory edema results with involvement of lymphatics and blood- 
vessels, by either of which routes the cocci get into the blood-stream. 
Serous membranes are especially susceptible to streptococci, and throm- 
bophlebitis or arteritis is the first lesion arising when the germ reaches 
a vessel. In these infections there is more often bacteremia than is the 
case with staphylococci. 

Injected into animals (intravenously) virulent streptococci may 
occasion septicemia, but it is notoriously difficult to obtain cultures 
of great virulence and the succeeding generations soon lose their power. 
White mice and rabbits are the most susceptible animals. 

A single attack of erysipelas or streptococcic infection confers no 
immunity on man and, similarly, one inoculation occasions no immunity 
in animals. By repeated injections, however, an antistreptococcus serum 
of some potency has been obtained. Recent studies show that more 
satisfactory practical results may be obtained when the antistrepto- 
coccus serum has been prepared with a strain of organisms similar to that 
present in the case under treatment. For this reason mixtures of serum 
prepared with several strains are used (polyvalent sera), so that in a 
clinical case (because of the difficulty in distinguishing various strains) a 
specifically active antiserum may be administered. The efficacy of such 
polyvalent sera, however, is somewhat doubtful. 

Streptococcus intracellularis meningitidis (Weichselbaum) . — This 
organism, also called meningococcus or Diplococcus meningitidis, is found 
in the meningeal pus, in the blood, nasal mucus, sputum, and urine of 
individuals affected with epidemic cerebrospinal meningitis. This 
micro-organism in some respects resembles very closely in its form and 
intracellular occurrence the gonococcus. 

The organism appears as a biscuit-shaped diplococcus, irregular in 
size, sometimes occurring as tetrads or in clumps, and occasionally as 
short chains in which the line of cleavage between the diplococci is in 
the same direction as that of the chain. The coccus is Gram-negative, 
but here and there will be found a few units that retain the blue of 
the gentian-violet. It is easily stained with Loffler's methylene-blue. 

In the meningeal exudates it is usually found within polymorpho- 
nuclear leukocytes, like the gonococcus. Some have described its 
occurrence within the cellular nuclei; this is doubtful. 

It grows well at 37.5° C. (100° F.) on blood-agar, serum-agar, and 
plain agar. On the latter there appear, in forty-eight hours, flat. 



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A TEXT-BOOK OF PATHOLOGY 



grayish-white, faintly granular and viscid colonies that do not coalesce. 
On blood-agar the colonies are more luxuriant. 

The cultures may live for weeks, but often die in a few days, and, 
therefore, require frequent transplantation. 

Distribution. — The meningococcus is found in the seropurulent 
exudate of epidemic cerebrospinal meningitis and is readily demon- 
strated in the fluid obtained by lumbar puncture. It has frequently 
been found in the nasal mucus of patients suffering from the disease 
and in healthy individuals more or less closely associated with the 
patient. The assumption is, that the meningeal infection occurs by 
passage of the organisms through the lymph-channels from the nose 
or sinuses adjacent to the meninges. Recent experiments seem to 
indicate that the organisms may travel in the opposite direction, for in 
monkeys infected by intradural inoculation the organisms were found 
in the nasal cavities after a short interval. Organisms resembling the 
meningococcus and probably actual meningococci have been found in 
the lungs in cases of bronchitis and pneumonia complicating epidemic 
meningitis. 

Pathological Physiology and Pathogenesis. — Large subcutaneous in- 
jections may cause death, and intrapleural and intraperitoneal injec- 
tions may kill animals and cause a fibrinopurulent inflammation of the 
serous membrane. Subdural inoculation (spinal and cerebral) in dogs 
and monkeys have caused lesions identical with those found in 
man. 

The toxins of the meningitis coccus are endocellular and are freed in 
vitro by autolysis. Agglutinins and lysins are developed in patients and 
experimental animals. Flexner, Jobling, and Wassermann have devel- 
oped an antiserum from goats which when used intraspinally dissolves 
the organisms. 

Other Organisms in Meningitis. — The pneumococcus, Streptococcus 
pyogenes, Staphylococcus pyogenes, typhoid and colon bacilli, influenza 
bacillus, and, less commonly, some other forms have been isolated in 
cases of primary meningitis or meningitis secondary to infection else- 
where. 

GONORRHEA 

Definition. — Gonorrhea is an infectious inflammation of the urethral 

or other mucous membranes due to a specific organism, the Micrococcus 
gonorrhoeae or gonococcus discovered by Neisser in 1879. 

Etiology. — There is no doubt that the gonococcus is the specific 
cause of gonorrhea. This organism is a micrococcus, usually arranged 
in pairs, the opposed surfaces of each being slightly concave. This 
arrangement has suggested the designation "biscuit-shaped" diplo- 
coccus (Fig. 101). Sometimes groups of four or more are found, while 
in other cases the cocci occur singly. The organisms are abundant 
in the pus of acute gonorrhea, less abundant in advanced stages, in the 
pus of gonorrheal salpingitis or other conditions, and may not be dis- 
covered at all. They generally occupy the pus-cells, lying in the proto- 



DISEASES DUE TO BACTERIA 



279 



plasm, either in small numbers or so abundantly as to fill the cell uni- 
formly. In the tissues the same intracellular position is usual, but here, 
as in the free pus, some organisms may generally be found between the 
cells. The gonococcus stains readily with ordinary solutions of anilin 
dyes, and is distinctly Gram-negative. 

Cultivation of the gonococcus is difficult. Growths may, however, 
be obtained at 37° C. (98.6° F.) upon agar-agar streaked with human 
blood or on media prepared from human ascitic or pleuritic fluid or 
albuminous urine. Later generations may grow well on ordinary media, 
but usually require the serum additions. The growth in blood-serum 
consists of small colonies of grayish color that coalesce and form a film 
on the surface of the medium; around the colony may generally be 
seen an irregular and inconspicuous extension. 

The gonococcus cannot be positively distinguished by its morphol- 
ogy nor by the intracellular position, 
stages of their growth show a typ- 
ical biscuit form (staphylococci and 
others) ; and the intracellular position 
is not rarely assumed by a variety 
of bacteria. The failure to stain by 
Gram's method and the failure to 
grow on ordinary media are strong 
points suggesting the gonococcus. 
Typical cultures alone establish the 
diagnosis. A number of organisms 
resembling the gonococcus were found 
by Bumm in the vaginal mucus. The 
Micrococcus catarrhalis also resembles 
it closely. No similar micrococcus 
has thus far been found in the male 
urethra. 

Pathogenicity. — It has been demonstrated by direct implantation 
of pure colonies upon the healthy urethra that this organism will cause 
characteristic gonorrhea. Urethritis may, however, be due to other 
organisms; the specific form termed "gonorrhea" is probably always due 
to the gonococcus. Secondary lesions, such as salpingitis, oophoritis, 
arthritis, peritonitis, conjunctivitis, endocarditis, etc., may also be due 
to this organism, no other form of bacteria being present. Sometimes, 
however, complications, such as periurethral abscesses, suppurative 
adenitis, etc.. are due to secondary infections. 

Gonococci stimulate the formation of slight amounts of agglutinins, 
opsonins, and bacteriolysin. Antisera are of little value, but bac- 
terins or vaccines may be Useful. The toxin is intracellular. 

Pathological Anatomy. — The lesions of gonorrhea will be considered 
elsewhere. Suffice it to say in this place that the organism causes sup- 
purative catarrh of the mucous surfaces with which it comes in contact. 
There is abundant cellular exudation and the organisms tend to pene- 
trate deeply into the tissues. 



Other organisms may in certain 




Fig. 101. — Pus from gonorrhea, showing 
gonococci (Jakob). 



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A TEXT-BOOK OF PATHOLOGY 



Pathological Physiology. — Gonorrhea is in most cases a purely local 
disease. Little is known of its power to produce soluble toxins. The 
effects are probably due to an intracellular toxin. The distant lesions 
are in all cases, as far as we definitely know, dependent upon trans- 
portation of the specific organism. These have been found in the 
effusions of arthritis, in meningeal exudates, and in the vegetations of 
gonococcal endocarditis, as well as in the blood in the last-named condi- 
tion. 

CROUPOUS PNEUMONIA 
Definition. — There are a number of forms of inflammation of the 
pulmonary tissues to which the term "pneumonia" is applicable. The 
most definite form of disease is that spoken of as croupous, fibrinous, or 
lobar pneumonia. In its typical form this is a specific and well charac- 
terized disease. It is infectious, more or less contagious, and caused 
by a specific organism. 

Etiology. — The organism most frequently found in the lung in 
croupous pneumonia and doubtless the specific cause of the disease in 
such cases is the Diplococcus •pneumonia, belonging to the genus Strepto- 
coccus. It is less regularly the etiological agent in bronchopneumonia 

and atypical pneumonias, but even 
in these cases it is found more fre- 
quently than other bacteria. 

The organism is also called the 
pneumococcus, the Micrococcus lan- 
ceolatus, and sometimes the Strep- 
tococcus pneumoniae seu lanceolatus. 
The diplococcus of pneumonia was 
recognized in the saliva of healthy 
persons by Sternberg and Pasteur, 
I " but its relation to croupous pneu- 

monia was first demonstrated by 
Frankel, and later by Weichsel- 
baum. The individual organism 
has a somewhat elongated, lanceo- 
late shape, and has, therefore, 
been considered a bacillus, though 
it does not always show this 
pseudobacillary shape distinctly (Fig. 102). In the sputum and 
lungs and in the blood of inoculated animals it is commonly found 
in pairs; the broader ends of the organisms adjacent, and the pointed 
ends projecting outward; the group is surrounded by a transparent 
capsule, which does not readily take stains and, therefore, becomes con- 
spicuous (Fig. 103). Sometimes the organism forms chains, in which, 
however, the pairs of micrococci are a little distance apart. Chain 
formation is especially marked when the organism is grown in fluid 
media. The capsule is not seen when the organism is obtained from 
cultures. The diplococcus does not possess individual motility and has 
no flagella. It does not seem to produce spores. 




Fig. 102. — Diplococcus pneumoniae in the 
blood (Frankel and Pfeiffer). 



DISEASES DUE TO BACTERIA 



281 



It may be readily demonstrated in the sputum or in the tissues by 
staining with the ordinary anilin dyes or by Gram's method. 

Cultivation. — The diplococcus grows readily upon ordinary media, 
excepting potato. It forms characteristic colonies upon agar-agar plates 
or in gelatin. Upon the surface of the agar there appear transparent 
drop-like colonies hardly visible to the naked eye, which under the 
microscope have a finely granular appearance. Upon gelatin plates 
similar growths are produced, while in gelatin punctures the growth 
occurs along the path of the wire as granular whitish spots separated 
from each other. The addition of serum or ascitic liquid to agar makes 
a medium in which larger and more conspicuous grayish colonies of 
circular outline appear on the surface. In the paler marginal zone of 
the colony, diplococci or short chains may be seen. On blood-agar 
pneumococci produce small round greenish colonies without hemolysis. 
In bouillon a cloudiness is produced when the 
culture is from twelve to twenty-four hours 
old; later the organisms precipitate and the 
bouillon becomes clear. Milk is acidified and 
at times coagulated by the pneumococcus. 
When inulin is added to a serum medium the 
pneumococcus ferments the inulin and coagu- 
lates the serum. The organism tends to die 
out very readily in cultures, and also loses its 
pathogenic property when propagated for 
several generations. In solid media contain- 
ing serum and more particularly in fluid media 
the virulence may be preserved for a long 
time, sometimes for months. It is most luxuriant at 37° C. (98.6° F.). 
Pneumococci are dissolved by bile or solutions of its salts, in this being 
different from the streptococci. 

Pathogenicity. — The specific character of this organism has not been 
definitely proved according to the rules of Koch, but it is highly probable 
that it is the usual cause of pneumonia. The diplococcus is frequently 
found in the saliva of healthy persons. When this is introduced into 
animals, particularly rabbits, the animal dies, with evidences of rapid 
sepsis (sputum septicemia). The postmortem shows some fibrinous 
exudate and occasionally a little pus at the point of inoculation. The 
spleen is enlarged, and capsulated bacteria of distinct lanceolate form are 
widespread throughout the body. Injections of lung tissue or of pneu- 
monic sputum produce similar results, and the organism in pure cul- 
ture likewise causes this form of septicemia. It has been shown that 
injection of pneumonic exudate aspirated from the consolidated lung 
into the lungs of rabbits will produce true pneumonia. Typical 
pneumonia has been produced by injection of virulent pneumo- 
cocci into the lungs of rabbits previously immunized against the 
pneumococcus to prevent the occurrence of general pneumococcus 
septicemia. 

The most successful attempts at producing pneumonia were made 




Fig. 103. — Diplococcus 
pneumonia : a, Cocci, with- 
out capsules; 6, single and 
paired cocci, with capsules; 
c, chain form; d, colony of 
cocci (Ziegler). 



282 



A TEXT-BOOK OF PATHOLOGY 



by Rosenau and later by Meltzer, who atomized pneumococcus cultures 
into the trachea of dogs. 

The toxin of the pneumococcus is intracellular. Some antibodies 
may be formed. 

Besides the diplococcus there are certainly other elements which 
contribute to the causation of the disease, else the frequent occurrence 
of the micro-organism in question in the saliva would make pneu- 
monia a much more common affection. The nature of the contributing 
causes is, however, obscure. Exposure to cold, general depression of the 
system, traumatism, alcoholism, and other causes certainly predispose 
or help to determine the occurrence of the disease. These causes may act 
by temporarily increasing the virulence of the diplococcus or by lower- 
ing the resistive power. 

Certain irregular forms of lobar pneumonia may be caused by 
streptococci, staphylococci, the Bacterium pneumoniae of Friedlander, 
the influenza bacillus, that of typhoid fever, etc.; but true croupous 
pneumonia is probably always due to the Diplococcus pneumonias. 

Pathological Anatomy. — (See Diseases of the Lungs.) 

Pathological Physiology. — The diplococcus produces, in the first 
place, local lesions of the lungs; and in the second place, systemic infection 
and possibly also general intoxication by toxins of uncertain character. 
The infection-atrium is almost always the respiratory tract. In the 
case of systemic infection the organism itself gains access to the blood 
and may produce secondary lesions in other organs. Infection with the 
diplococcus of pneumonia causes a pronounced reaction on the part of 
the blood in the form of leukocytosis. This is not invariable, but is 
usually seen. After the attack of pneumonia there is temporary im- 
munity, and it has been found that animals may be immunized for con- 
siderable lengths of time by repeated injection of pneumococci. The 
serum of the immunized animal has a certain protective and curative 
value which has recently been attributed to the formation of opsonins, 
which are operative by rendering the pneumococci liable to rapid 
ingestion by phagocytes. 

There are several varieties of the pneumonia coccus with slightly 
differing biological characters, and it may not be possible to obtain a 
therapeutic antiserum against them all. Gole insists that a polyvalent 
serum will not answer, but that one should use an antiserum against the 
type of pneumococcus present in each individual case. The antiserum 
supplies immune bodies including, perhaps, antitoxin. The author 
just mentioned has been able to divide the pneumococci into four 
main groups into which practically all strains fall. For two of these 
he has a separate antiserum. It has also been possible to use with 
advantage as a therapeutic agent autolysates of pneumococcus cul- 
tures at that stage of autolysis when the specific protein is freed. 

The Diplococcus in Other Diseases. — The Diplococcus pneumoniae 
has been found in various conditions complicating pneumonia, and 
occasionally in lesions unassociated with croupous pneumonia. Among 
other lesions, meningitis, pleurisy, and other inflammations of the 



DISEASES DUE TO BACTERIA 



283 



serous surfaces, abscesses, otitis media, and arthritis have been found 
to be due to this organism; or, at least, this organism alone has been 
found in some of these cases. Endocarditis is frequently caused by 
the pneumococcus. It may be primary or secondary. 



OTHER FORMS OF PNEUMONIA 



Among other varieties of pneumonia may be mentioned the catar 
rhal or lobular form, the tuberculous form, and various irregular pneu 
monias, partly cellular, partly fibrinous, partly 
purulent or hemorrhagic. Though the pneumo- 
coccus is more frequently present than any other 
single organism in bronchopneumonias after in- 
fectious diseases like measles and diphtheria and 
in various irregular types of bronchopneumonia, 
different organisms may be found in such cases, 
and some of these may be of etiologic importance 
in certain cases. Not rarely the pulmonary 
disease is the result of mixed (double or multiple) infection. 

Bacterium pneumoniae of Friedlander. — This organism was re- 
garded at one time as the cause of croupous pneumonia. It prob- 




Fig. 104. — Bacterium 
pneumoniae of Fried- 
lander. 




Fig. 105. — Friedlander's pneumonia, showing the enormous number of bacteria in the 

exudate. 



ably occurs in most cases as a mixed infection, though it may occa- 
sionally be the cause of catarrhal or irregular forms of pneumonia or of 
ordinary croupous pneumonia. With this organism also Meltzer has 
been able to produce pneumonia in dogs by atomized insufflation. 



284 



A TEXT-BOOK OF PATHOLOGY 



The cases of pneumonia due primarily to the pneumobaeillus are char- 
acterized by their virulence and a peculiar viscid character of the 
exudate in the lung. Friedlander's organism occurs as a distinct bacil- 
lus, usually in pairs and surrounded by a capsule like that of the diplo- 
coccus (Fig. 104). Sometimes it may form chains of three, four, or 
more organisms. It stains well with the anilin dyes, but is decolorized 
by Gram's method. A characteristic culture is obtained in gelatin. 
The puncture-culture is characterized by a luxuriant growth at the 
top and a considerable vegetation all along the track. This leads to a 
nail-shaped growth. The gelatin does not liquefy. Upon agar a con- 
siderable whitish or yellowish moist growth occurs upon the surface. 
There is formation of gas in media containing glucose, and often also 
on potato. 

A number of organisms closely related to Friedlander's pneumo- 
baeillus have been classified under the generic name Bacterium muco- 
sum capsulatum. Among these are the B. lactis aerogenes, B. acidi 
lactici, B. ozoence, and B. rhinoscleromatis. The several types differ some- 
what in their power to ferment various carbohydrates. 

Other Organisms in Pneumonia. — Among the various organisms 
that have been found in bronchopneumonia or less commonly fibrinous 
pneumonia are the Streptococcus pyogenes, more rarely the influenza 
bacillus, the Bacillus coli communis, the typhoid bacillus, the bacillus 
of glanders, of the plague, and occasionally other organisms. In some 
of these cases the disease may be the result of double infection. 

Tubercle Bacillus. — A uniform pneumonic process may be due to 
simple infection with the tubercle bacillus, or to mixed infections. 

Micrococcus tetragenus. — This form is a Gram-positive micrococcus 
from 1 to 2 (J. in diameter, and receives its name from the peculiar asso- 
ciation in groups of four. It occurs in the sputum and contents of 
cavities in pulmonary phthisis, and occasionally elsewhere. It may 
give rise to general sepsis. 

Micrococcus catarrhalis is a micro-organism found by Pfeiffer in 
cases of bronchitis in which there was a great deal of expectoration, and 
in which the symptoms resembled those of influenza. It is a small 
coccus, usually occurring in diplococcic form, and resembling the micro- 
coccus of gonorrhea. It often is seen within the pus-cells, and occurs in 
large numbers in the sputum and nasal secretion of individuals suffering 
from bronchitis. It does not cause the constitutional disturbance that 
is caused by the bacillus of influenza, but is often found as an associated 
infective agent in cases of pneumonia due either to the Diplococcus 
pneumonia? or to the bacillus of influenza. To obtain it in pure culture 
it is best grown on blood-agar. It grows as sharply defined, somewhat 
raised, granular, yellowish, non-transparent colonies on the surface of 
agar. It resembles the Staphylococcus .pyogenes aureus, but the colonies 
are much more raised and harder. They can be picked up on the end of 
the needle, and are crushed with difficulty. The needle can be drawn 
across the culture without destroying the integrity of the individual 
colonies. After the first generation the micrococcus grows well on 



DISEASES DUE TO BACTERIA 



285 



ordinary agar, but it must be transferred every three or four days to 
be kept alive. It is decolorized by Gram's method. Its pathogenicity 
is as yet undetermined. In its behavior toward animals it resembles 
the bacillus of influenza. It seems to be of importance in the pneumo- 
coccal or streptococcal anginse, since, according to the work of one of 
the authors, a culture of one of these cocci is much increased in patho- 
genicity for guinea-pigs when mixed with Micrococcus catarrhalis. 

Diseases Due to Bacillary Forms 
diphtheria 

Definition. — Diphtheria is an infectious and contagious disease 
caused by a specific bacillus. 

Etiology. — The Bacterium diphtheria was discovered by Klebs, but 
more accurately studied by Loffier, and is, therefore, called the Klebs- 
Loffler bacillus. This organism is a rod varying in length from 1 to 6 n, 
rather thick, and with somewhat swollen ends. It is readily demon- 




Fig. 106. — Diphtheria bacilli from an eighteen-hour blood-serum culture. 

strated in the local lesions of the mucous membranes or skin, where it 
may be quite abundant; the individual bacilli, however, are separate 
from one another. The organism is peculiar in its great irregularity 
of shape and size, particularly in cultures (Fig. 106). Seemingly 
branched forms have been observed, and some investigators have viewed 
the organism as a streptothrix or even as one of the hyphomycetes. 



286 



A TEXT-BOOK OF PATHOLOGY 



Frequently one end is especially large, giving a club-shaped appear- 
ance; some of the bacilli are very large; some present rounded granules 
at either end, the so-called polar granules or Ernst bodies. The bacillus 
is readily stained with aqueous solutions of basic stains, especially with 
those rendered slightly alkaline. (LofHer's solution — saturated aqueous 
solution of methylene-blue, 30 c.c, in aqueous solution of potassium 
hydrate, 1 : 10,000, 100 c.c. — is the favorite stain.) The color is retained 
when stained by Gram's method. The stained specimen shows the mor- 
phology of the bacillus very clearly. The rounded ends generally stain 
more deeply than the shaft of the bacillus, so that the appearance 
somewhat suggests a diplococcus, or as a row of cocci. Not rarely 
transverse fractures give the organism the appearance of disjointed 
segments. There are no flagella, and the bacillus is not motile. Spores 
have not been demonstrated. 

Cultivation. — The most characteristic cultures are obtained upon 
blood-serum, especially such as contain a small amount of glucose. Upon 
this medium there is formed within six, twelve, or twenty-four hours a 
thin, whitish or yellowish-white layer of irregular outline, often showing 
separate smaller colonies around the edge. A small portion of the 
colony may be removed and stained, and the diagnosis thus established 
with ease in a short time. Other organisms found in the throat are 
slower in growth, and do not, therefore, interfere with the diagnosis. 

Pathogenicity. — When cultures in bouillon are injected beneath 
the skin of a guinea-pig a fibrinous inflammation with more or less 
widespread edema results, and the animal dies in from twenty-four to 
thirty-six hours. Congestion of the adrenal, necrotic foci in the liver 
and other organs are found postmortem; the neighboring lymphatic 
glands are enlarged. If the animal survive, paralysis may make its 
appearance, as in human beings recovering from the disease. The 
pathogenicity has also been shown by inoculation of various other 
animals, and definitely by accidental infection of man. 

Klebs-Lofner bacilli may be found in the pharynx of a person show- 
ing no indication of disease. This indicates that the organism has not 
found a favorable soil for its development or no abrasion or opening 
into tissues that will support its growth. The bacillus may, however, 
thrive and multiply for a considerable time upon the mucous membrane 
of such a throat, as it may upon food, clothing, or other infected mate- 
rials. 

Mixed Infection in Diphtheria. — Other organisms, notably strep- 
tococci, staphylococci, and pneumococci, may be associated with the 
diphtheria bacillus, and may be actively concerned in the local or 
general pathological processes. The streptococcus is especially potent 
as an associated cause. The streptococcic infection may precede or 
follow the diphtheritic infection. Various organisms of a saprophytic 
nature may cause putrefactive changes in the pseudomembrane. 

Predisposing Causes. — Some predisposition is necessary for the 
development of the disease. In part this is personal, some individuals 
being highly susceptible, others scarcely at all. In part, accidental 



DISEASES DUE TO BACTERIA 



287 



conditions, such as pharyngitis, laryngitis, abrasions, etc., furnish a 
favorable opportunity for the infection. 

The diphtheria of birds, calves, and certain other animals is distinct 
from the human disease; and the organisms are in no way related. 
Human diphtheria may occur in cats, and these animals may propagate 
epidemics. 

Pseudomembranous (fibrinous) inflammation is not invariably caused 
by the diphtheria bacillus (see Inflammation). Among the organisms 
capable of causing somewhat similar pseudomembranes, the most fre- 
quent is the Streptococcus pyogenes ; another important one is the 
pneumococcus. 

Distribution of the Bacilli. — The organisms are abundant in the 
pseudomembranes of diphtheria, but are only exceptionally found 
in the blood or internal organs. The visceral or nerve lesions are usually 
due to the toxins, and not to the bacillus. The same is true of experi- 
mental diphtheria. The internal lesions may be produced by injection 
of the toxin obtained by filtering a bouillon-culture through a Pasteur 
filter. 

Pathological Anatomy. — Diphtheria is primarily a local disease of 
the pharynx (pharyngeal), of the larynx (laryngeal), of the nose (nasal), 
or of the skin (dermal). The bacillus lodges in the mucous membrane 
or skin, and produces a pseudomembrane. This consists of fibrinous 
exudation in the form of fine granular material or a fibrillar network, 
in which are embedded the epithelial cells and other tissue elements 
and infiltrating leukocytes. The epithelial cells rapidly undergo coagu- 
lation necrosis or granular degeneration, as do also the connective 
tissues when the process extends beneath the mucosa. The blood-vessels 
become obstructed by thrombosis or compression, and the tissue is, 
therefore, avascular. Nearly always the pseudomembrane thus formed 
is attached to the underlying tissues, and when removed a raw and 
bleeding surface is exposed. The depth of involvement, however, 
varies; sometimes the submucosa is soon involved; more often the 
disease is practically confined to the mucosa. 

The macroscopical appearance is that of a whitish, dirty-yellowish, 
or brownish membrane upon the mucous lining of the throat. This 
begins as one or several patches upon the tonsil, and spreads rapidly to 
the neighboring parts. In other situations the appearance is much the 
same. Inflammatory swelling beneath and around the diseased area is 
habitual. It is of great clinical importance to recognize that true diph- 
theria may occur in the form of typical follicular tonsillitis. 

Internal or visceral lesions may occur in the course of diphtheria or 
during convalescence. They are usually due to the action of the toxin, 
and not of the bacillus. Necrotic foci in the liver, showing advanced cell- 
ular degeneration of the cells with hyperchromatosis of the nuclei, and 
similar lesions of other organs, may be seen in the human body, as in 
animals killed with the organism or its toxin. Swelling of lymph-tissue 
is common, the principal point of attack being endothelium. This 
may go on to focal necrosis. Myocarditis and myocardial degenera- 



288 



A TEXT-BOOK OF PATHOLOGY 



tion, renal degeneration and nephritis, and, most interesting of all, de- 
generation of the peripheral nerves and neuritis may be met with. 
All of these will be described elsewhere. This is believed to be due to 
the toxone fraction of the toxin. 

Pathological Physiology. — x\s has been said, the disease is pri- 
marily local, and the bacilli nearly always remain localized in the 
superficial lesions. They have been found in the internal organs, 
showing that they can enter the blood-stream. The local effects 
are believed by some to be due to an endocellular toxin. The 
general manifestations — fever, prostration, and the visceral lesions — 
are caused by poisonous substances elaborated by the growth of the 
bacilli. There are probably several substances of this sort, but one in 
particular — the toxin — is most important. This may be obtained by 
filtering bouillon-cultures through porcelain, and by its injection the 
constitutional and some of the local manifestations of the disease may 
be induced in animals. Successive introduction of increasing doses of 
toxin causes the development of antitoxic substances that may finally 
accumulate in the blood to such extent that the animal becomes immune 
to the most virulent bacilli. The antitoxic substance or substances, or 
antitoxin, found in the blood and the blood-serum of immunized animals 
will render other animals immune for a time, or combat and overcome 
the disease if already existing. Simultaneous injection of antitoxin and 
of many times the ordinarily fatal dose of toxin or diphtheria-cultures 
leaves an animal unharmed. The value of the antitoxin in animal 
experimentation is beyond doubt. In the human being there is scarcely 
any doubt of its potency, though, of course, crucial experiments cannot 
be made. Experience has shown that its therapeutic use in diphtheria 
should never be omitted. 

After an attack of diphtheria there is temporary immunity, but this 
passes off and successive attacks may thus occur in the same person. 

Diphtheria=like bacilli are sometimes found in the pharynx of 
healthy individuals in some cases, as well as upon the hands, hair, or in 
other parts of the body. They are also found in various forms of rhinitis, 
conjunctivitis, and non-diphtheritic angina. These may differ from the 
virulent bacilli in being somewhat shorter and in growing more lux- 
uriantly. Their distinctive character, however, is their relative harm- 
lessness when injected into animals. 

Pathogenic powers have been ascribed to certain members of the 
pseudodiphtheria group of bacteria. Some seem to be able to pro- 
duce a transmissible angina that is not favorably influenced by diph- 
theria antitoxin. Others of the group may cause general infection or 
severe local disturbance. 

The exact relationship of the members of the diphtheria group is 
not yet decided, but the classification of Emerson is quite good: 

"(1) Bacilli with typical morphology, typical cultural characteris- 
tics, especially the ability to form acid from glucose, and which produce 
the typical lesions in animals, are, in the opinion of all observers, Bacillus 
diphtheria?. 



DISEASES DUE TO BACTERIA 



289 



"(2) Bacilli with typical morphology and typical cultural reac- 
tions, especially the ability to form acid from glucose, but which are 
not pathogenic to animals, may be called avirulent diphtheria bacilli. 

"(3) Bacilli with typical morphology, but which do not conform in 
their cultural reaction with the diphtheria bacillus, and which are not 
pathogenic for animals or do not produce typical lesions, may properly 
be called pseudodiphtheria bacilli. 

"(4) Finally, there are a number of organisms which resemble 
Bacillus diphtherial in many ways, but whose morphology is not ex- 
actly the same, . . . and which have different cultural characteristics, 
and differ in their pathogenicity. This group certainly includes the 
pseudodiphtheria bacillus of Hoffmann, the xerosis bacillus, and others." 

The pathogenic members belong in the first and third or possibly the 
second and third groups. A difference of the pseudo- and true diph- 
theria bacilli not mentioned above is that the former do not produce a 
soluble toxin, but upon injection excite a bactericidal serum in experi- 
mental animals specific for each variety. The so-called virulent pseudo- 
diphtheria bacilli have been found in cystitis, septicemia, and other 
conditions. They are very common in mixed infections, and have 
been said to be more potent in continuing an infection than in inciting it. 

TYPHOID FEVER 

Definition. — Typhoid fever is an infectious disease, with char- 
acteristic lesions of the intestines, and due to a specific bacillus. It is 
important to recall the fact that local or general typhoid infection may 
occur without the intestinal lesions or usual clinical features of typhoid 
fever. In such cases local inflammatory lesions, suppurations, necroses, 
or septicemia have been observed. 

Etiology. — Certain predisposing features make individuals more 
liable at one time than another to this disease. It occurs in adoles- 
cence and the young, but rarely in the old. Climatic conditions are 
supposed to play some part, and doubtless do have an influence. Ty- 
phoid fever is especially a disease of the temperate zones, and is most 
abundant in the autumn. Drainage and other conditions affecting the 
surroundings of persons may influence the predisposition. One attack 
usually confers immunity for the rest of life; exceptions, however, are, 
met with. 

The Bacillus. — The Bacillus typhi abdominalis, the specific organism, 
was discovered by Eberth and isolated by Gaffky. It is a short bacillus, 
from 1 to 4 u in length and 0.5 to 0.8 [i in thickness. The ends are rounded 
and often somewhat plump. In culture these rods or bacilli occasionally 
form long chains, but in the tissues they are never so arranged. The 
organism is actively motile, this being due to flagella, of which there are 
eighteen or twenty attached to the periphery (Fig. 107). When stained 
with alkaline methylene-blue or other stains there are sometimes seen 
dark-colored spots at the ends of the organism. These were formerly 
regarded as spores, but are now recognized as areas of protoplasmic 

19 



290 



A TEXT-BOOK OF PATHOLOGY 



condensation. Under certain circumstances the condensation is seen 
in the center and vacuole-like formations are found at the ends. The 
organism is readily stained, but decolorizes very easily, and is, therefore, 
difficult to demonstrate in tissue. The bacilli are, as a rule, found in 
clusters. These groups may, however, be few in number, and thus 
difficult to detect in the organs. 

Cultivation. — Artificial cultures of the bacillus have been obtained 
from the spleen and other organs, as well as directly from the blood, 
stools, and urine of patients suffering from the disease. They grow 
very well upon the ordinary culture-media, such as agar-agar, gelatin, 
and potato, the temperature of the body being most favorable, but some 
growth occurs at the ordinary temperature of the room. Upon gelatin 
and agar there are formed irregularly whitish films, which on close 
inspection with the lens show a granular appearance. This growth, 




Fig. 107. — Bacillus typhi abdominalis, from an agar-agar culture six hours old, showing the 
flagella stained by Loffler's method; X 1000 (Frankel and Pfeiffer). 

however, is not distinctive. Upon acid potato a characteristic transpar- 
ent pellicle is formed. This may be invisible except to the trained eye, 
but on scraping the surface with a platinum wire the pellicle can be 
raised, and on microscopical examination it is found to be composed of 
bacilli. Sometimes the pellicle is yellowish or brownish. When culti- 
vated in milk there is slight acidity, but coagulation does not occur. 
When grown in agar containing a little glucose no fermentative gas 
results. Another feature of importance is the absence of indol reaction, 
the addition of potassium nitrite and sulphuric acid to bouillon-cultures 
causing no rose color, such as occurs with some other organisms. 

The biological characters of the typhoid bacillus are distinct enough 
when isolated, but as it occurs so frequently in company with the colon 
bacillus, whose colonies are similar, numerous technics have been 
devised for its isolation. These must be studied in books on bacte- 



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291 



riology. (Compare Cultivation of Typhoid and Colon Bacilli, pages 290 
and 296.) One of the most reliable tests for the identification of the 
typhoid bacillus is the Widal reaction, the clumping of the organism 
by the blood of typhoid patients, or, better, by the serum of animals 
immunized against a known culture of the Bacillus typhosus. Human 
typhoid serum may clump colon bacilli also in low dilutions. 

Pathogenicity. — Animal experimentation has thus far been unsat- 
isfactory. A few observers have succeeded in producing illness and 
intestinal lesions by feeding animals with typhoid cultures, particularly 
after the stomach and intestines have been rendered alkaline with 
soda and peristalsis has been checked with opium. In most cases in- 
jection of the typhoid bacillus has produced septicemic manifestations. 
The anthropoid apes have been infected by feeding and injection with 
typhoid bacilli, the resulting intestinal and other lesions bearing a rather 
distinct similarity to those in man's natural disease. The constant 
occurrence of the germ, its absence from other conditions, and the 
absence of any other germ as a constant accompaniment of typhoid 
fever, have led to the general acceptation of this as the specific cause. 
Moreover, its properties are such that the spread of the disease in the 
acknowledged ways is entirely compatible with the acceptance of the 
bacillus as the specific cause. 

Distribution. — The typhoid bacillus occurs both within and without 
the human body, and doubtless multiplies greatly in the external 
world when the conditions are favorable. It is found with great regu- 
larity in the blood of typhoid patients, especially in the first week of 
the disease. It occurs in the lesions of the intestines and in the intes- 
tinal contents, especially during the second and third weeks of the 
disease. It is usually less abundant, but often present in the spleen, 
liver, and kidneys; it may occur in considerable abundance in these 
organs when there are local complications. It is almost always present 
in the gall-bladder in cases of typhoid fever, and frequently occasions 
cholecystitis and not rarely initiates the formation of gall-stones. 
It also occurs in the lungs, in the parotid gland, and in other organs, 
and posttyphoidal abscesses may contain the organism in abundance. 
Complicating lesions of other organs may be dependent solely upon 
the specific bacillus, it being capable even of acting as a pyogenic organ- 
ism, or they may be dependent upon secondary or mixed infections. 

The typhoid bacillus is peculiarly resistant, and may thrive upon 
clothing, in soil, and in water for a long time. Cold has no effect, the 
germ being virulent after freezing and thawing. It has rather more 
resistance to carbolic acid than other members of the typhocolon 
group. These features help to explain the spread of the disease and its 
general prevalence. The organisms are discharged from the body of a 
patient suffering from the disease mainly in the stools, but in part also 
in the urine, sweat, and other excreta. If they are not at once destroyed, 
contamination of clothing, soil, water, etc., may occur, and subsequent 
infection of susceptible individuals takes place through drinking-water 
or food with which the infected water or other matters have come in 



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contact. It is possible that infection may occasionally take place 
through the lungs by inhalation of dust. This must be very rare. Intra- 
uterine infection undoubtedly occurs in some instances in which the 
mother is suffering from typhoid fever. 

One means of transmission of typhoid is by means of "carriers." 
Carriers are persons who after recovery from a typhoid infection harbor 
somewhere within themselves virulent bacilli without active evidence 
thereof. They are usually in the gall-bladder, but may be in lymph- 
nodes or liver. They may be excreted and pollute water or surrounding 
objects. The reason for this carrying of germs may lie in the fact that 
their focus is protected from the antibodies of the blood, or they may be 
"fast" strains. 

Pathological Anatomy. — The lesions of typhoid fever are con- 
sidered with the diseases of the intestines. It is important, however, 
to add in this place that widespread changes may occur in this disease 
as a result of the action of the bacillus. Thus there may be focal 
necroses in the spleen and liver, degenerative changes in the kidneys 
and muscles, and inflammatory changes in various glandular organs, 
the periosteum, the bones, or the connective tissues, the result of the 
direct action of the bacillus. There is a reaction on the part of lymph- 
adenoid tissue everywhere throughout the body, including all organs, 
even the larynx, in which definite lymphoid swellings occur in the 
mucosa, at times leading to ulceration. 

Pathological Physiology. — The typhoid bacillus elaborates toxic 
substances which give rise to fever and other general symptoms as 
well as to local lesions. Brieger and Frankel claim to have separated a 
specific toxalbumin. Whether this be the poison or not, there is no 
doubt that some form of a toxic body is present, and is endotoxic, not 
extracellular. During the existence of the disease the system reacts, 
in some way as yet unknown, to check its progress and to bring it to a 
termination at the end of four weeks, and lasting immunity is usually 
conferred. Whether or not there are distinct antitoxic substances 
remains to be determined. 

Protective vaccination with killed typhoid bacilli has been practised. 
The results of the English and American armies are most encourag- 
ing. Both the morbidity and mortality have been reduced. Russel, 
of the United States Army, concludes that it is a harmless efficient 
protection against infection and carriers, seldom giving any dis- 
comfort, and resulting in an immunity that probably lasts over two 
years. 

Vaccination treatment has been tried during an attack, but with 
indifferent results. No efficient antiserum has been found. 

Agglutination; Gruber-Durham Phenomenon; Widal Reaction. — 
This reaction is due to the presence, in the serum of inoculated animals 
or in that of man, of a substance capable of causing massing together 
and loss of motility of the specific micro-organisms concerned in the 
infection from which the animal or man furnishing the serum is suffering. 
This phenomenon may be studied macroscopically or microscopically. 



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293 



Macroscopically, we speak of a positive reaction when a distinct sedi- 
ment is seen in the glass containing the culture in a liquid medium, while 
the rest of the fluid remains clear, whereas before the phenomenon has 
taken place the whole fluid has had a diffuse cloudiness. Microscopically, 
we speak of a positive reaction when there occur a clumping and loss of 
motility of the bacteria, and, at the same time, the control remains 
free from all massing together. A certain amount of spontaneous 
clumping often occurs in the controls, but the organisms in the clump 
still exhibit motility, or there are actively motile individuals at the 
periphery or a little separated from it. Agglutination has been studied 
in reference to the bacilli of typhoid fever, plague, cholera, diphtheria, 
paratyphoid bacilli, the colon bacillus, proteus, and pyocyaneus. In 
order to obtain agglutination of the diphtheria bacillus it is necessary 
to immunize an animal highly with the bacteria themselves. The 
agglutination reaction is considered specific, except in the case of the 
colon group and proteus. With these two bacilli it is necessary to use 
the same strain of bacteria with which the animal has been immunized. 
Agglutination has also been studied with tubercle bacilli, but in this 
case it is necessary to destroy all the natural clumping of the bacilli by 
means of shaking with porcelain balls and then filtering. 

In studying agglutination with special reference to the Widal reaction, 
the best results are obtained when one always uses a definite quantity of 
the culture with a definite quantity of the serum. Cultures grown at 
temperatures of 25° to 35° C. (77°-95° F.) are better adapted to the reac- 
tion than those grown at 37° C. (98.6° F.). The more virulent the cul- 
ture, the less readily is agglutination obtained. In reference to typhoid 
bacilli, it is true that a twenty-four-hour culture is the best, since in 
older cultures pseudo-agglutination shows itself more readily. Widal and 
Foerster found no difference in the agglutinating properties of typhoid 
bacilli which had been formalized five months previously from the 
agglutination seen in fresh cultures. The time that it takes for agglu- 
tination to occur is dependent upon the activity of the serum and upon 
the temperature. At what day after the last injection in the immuni- 
zation of an animal the agglutination will appear, or at what day after 
the beginning of the disease in man agglutinin will first show itself, 
cannot be determined definitely. In men who are ill with typhoid 
fever the reaction has been demonstrated as early as the third day 
after the first appearance of the disease, but is often delayed much 
longer. Agglutinin remains in the blood for varying periods. In chil- 
dren recovering from typhoid fever the average time has been about 
two months after the convalescence ; in adults the average length of time 
is half a year. In the differentiation between the typhoid and coli 
bacilli by agglutination a very active serum is necessary. By im- 
munizing an animal with typhoid bacilli we can obtain a serum which 
will agglutinate both the typhoid bacilli and the colon bacilli, but this 
occurs in different dilutions. With the typhoid bacilli the dilution 
may be as high as 1 : 40,000 or 1 : 100,000, while with the coli the highest 
effective dilution will probably be 1 : 2000. The explanation of this is 



294 



A TEXT-BOOK OF PATHOLOGY 



that there are group agglutinins which have a certain effect on any one 
of a group of allied but not identical organisms, and possibly even the 
specific agglutinins have a certain limited effect (shown when the dilu- 
tion is not high) on other organisms than those for which they are specific. 

In the clinical use of the test the dilution of the serum should be not 
less than 1 : 50. An active serum will respond very quickly with dilu- 
tions of 1 : 100 or more. 

Concerning the nature of agglutinin, we note that it probably 
has a relation with globulin. It can be precipitated by magnesium 
sulphate. It is destroyed by heating to 70° C. (158° F.). The reaction 
is regarded by some German authors as being analogous to the phe- 
nomenon of coagulation, since the presence of salts is necessary. 

This reaction was found in 2283 cases of typhoid fever reported 
by various writers, and was absent in 109 cases of typhoid fever. It 
was absent in 1365 non-typhoid cases, and present in 22 non-typhoid 
patients. It was, therefore, found in 95.5 per cent, of the typhoid cases, 
and was absent in 98.4 per cent, of the non-typhoid cases; or, taking the 
entire 3779 cases, the correct result for diagnosis was arrived at in 96.5 
per cent. The reaction sometimes persists for some years after the 
attack of typhoid fever. Sometimes it occurs in cases in which there is 
typhoid infection without typhoid fever in the ordinary sense. These 
facts may explain some of the positive results obtained in non-typhoid 
cases. (See also Immunity.) 

Paracolon Infection; Paratyphoid Infection. — This is an acute infec- 
tion appearing sporadically and in epidemics resembling typhoid 
fever clinically, but in which the Widal reaction is persistently 
absent, and in which bacilli closely resembling the typhoid or colon 
bacilli, though differing in some essential particulars, are isolated 
from the blood and tissues. The intermediate organisms here referred 
to differ from the bacillus of typhoid by their ability to produce gas 
in glucose-containing media, and to produce an alkaline reaction in 
some media. They differ from the Bacillus coli communis by not 
coagulating milk, hot fermenting lactose, and by failing to form indol. 
The group of intermediates has been divided into a paracolon and a 
paratyphoid group, according to the closer resemblance to the colon 
group on the one hand or the typhoid bacillus on the other. The 
paratyphoids have been divided by Schottmuller into "A" and "B" 
groups, depending upon the acid reaction in milk. The 'A" strains 
are biologically nearer the bacillus of Eberth, while the "B" organisms 
are nearer the paracolons. Infections with the "B" paratyphoid 
bacillus outnumber those with "A." Members of the paracolon group 
are less closely related — as, for example, in the matter of interagglutina- 
tion — than those of the paratyphoid group. 

The paratyphoids give rise to a milder form of infection than typhoid 
fever, but the condition is transmissible in the same manner. The 
diagnosis is to be made by differential agglutinin tests when the bacillus 
cannot be isolated from the case. 

The paracolons are closely allied to the Bacillus psittacosis of 



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295 



Nocard, the B. icteroides of Sanarelli, the bacillus of hog-cholera, the 
B. enteritidis of Gartner 1 (meat-poisoning bacillus), and the B. dysen- 
teries of Shiga. The B. f cecal is alkdligenes of Petrushki is nearly related 
and sometimes causes typhoid-like infection, but it does not belong to 
the group. 

Pathological Anatomy. — H. G. Wells and L. O. Scott (1903) summarize 
the pathological findings in 5 cases of fatal paratyphoid infection, the 
cases of Strong, Longcope, Sion and Negel, Lucksch, and their own. 
The most constant change is splenic enlargement, which is in all re- 
spects the same as that of typhoid fever or septicemia. The endothelial 
cells are loaded with pigment evidently the result of hemolysis. 

Intestinal Lesions. — In Longcope's and Strong's cases the intes- 
tines were quite unaffected; in the other three, ulcerations resembling 
those of dysentery rather than those of typhoid fever were discovered. 
Peyer's patches and the solitary follicles were practically unaffected, 
as were also the mesenteric glands. In no case was there generalized 
glandular hyperplasia. 

In the cases of Longcope and AVells and Scott focal necroses in the 
liver, differing from those of typhoid in not containing endothelial cells, 
were found. The changes of proliferation and phagocytosis described 
by Mallory for typhoid fever were almost entirely absent in the intes- 
tinal lesions and very slight in the mesenteric glands, not being more 
conspicuous than that seen in simple enteritis. 

The anatomical picture was that of a septicemia with splenic enlarge- 
ment and occasionally non-specific ulceration in the intestines. The 
escape of Peyer's patches suggests an essential if obscure biological dif- 
ference between the typhoid and paratyphoid organisms. 

Nature of Paratyphoid Infection. — The tendency of most pathol- 
ogists at the present time is to regard paratyphoid infection as distinct 
in a bacteriological sense rather than in a clinical or general pathological 
sense, in the same way as pneumonias of varying bacteriology are dis- 
tinguished only etiologically. 

It cannot be denied that there are decided pathological differences, 
but the practical clinical identity and the near relationship of the bac- 
terial agents warrant the classification of paratyphoid infection as a 
subvariety of typhoid infection and the rejection of the term "para- 
typhoid fever" as significant of a separate disease. 

BACILLUS COLI COMMUNIS 

Synonyms. — Bacterium coli commune. It is customary to speak 
of the "colon group," since it has been recognized that several and per- 
haps many forms, varying in their ferment action only, have been 
classed under the name Bacillus coli communis. A number of organ- 
isms described under different names are probably identical. Among 
these are Bacillus neapolitanus of Emmerich, B. pyogenes fostidus of 
Passet. Several other organisms are either closely allied or identical. 

1 Gartner's Bacillus enteritidis has characters somewhat aberrant from the type here 
discussed. (See p. 37.) 



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Morphology. — The Bacillus coli communis is an organism almost 
exactly like the typhoid bacillus in appearance. It is rod shaped, but 
sometimes elongated and filamentous; at other times (young forms) 
short and rather rounded — coccus-like. It is motile, and has flagella 
attached to the periphery of the bacillus. The flagella are shorter, more 
slender, and less numerous than those of Eberth's bacillus (three to 
ten in number), and the motility of the organism is less uniform and 
active. It may be stained by ordinary solutions of anilin dyes, particu- 
larly with alkaline or carbolized solutions. It is decolorized by Gram's 
staining method. The stained bacillus shows light-colored or unstained 
portions like those of the typhoid bacillus. True spores have not been 
detected. 

Cultivation. — The organism grows luxuriantly upon ordinary 
media. The most distinctive growth is obtained upon acid potato. 
An elevated brownish colony is produced, which is usually easily dis- 
tinguished from the typhoid culture in the same medium. When culti- 
vated in gelatin or agar containing glucose, active gas production results. 
In liquid media (bouillon) a peculiar odor is developed. Addition of 
nitrites and pure hydrochloric or sulphuric acid causes a rose-red color 
— indol reaction. Milk is readily coagulated, partly as a result of acid 
formation and partly by the elaboration of a coagulating ferment. 

Distribution and Pathogenicity. — The colon bacillus is a normal 
inhabitant of the gastro-intestinal tract. It seems to exercise a bene- 
ficial effect in restraining (by its own active growth and acid formation) 
the growth of putrefactive and possibly pathogenic organisms. In 
certain inflammatory diseases of the intestines, however, it seems to 
increase in numbers and doubtless also in virulence. The organism may 
be found outside the body in various situations, particularly in water. 

The Bacillus coli is capable of producing inflammatory conditions 
in different situations. Injected into the peritoneal cavity of animals it 
gives rise to acute fibrinopurulent peritonitis, and in other parts of the 
body has analogous effects. 

It has been found in various diseases of the gastro-intestinal tract, of 
the biliary passages, of the urinary system, and of other parts, and is 
doubtless the direct cause of some of these, as the conditions present 
are practically the same as those produced by experimental inoculation 
of pure cultures. 

The lesions in the liver may be necrotic, or interstitial or catarrhal in- 
flammation. Colon bacilli are said to precipitate bile-salts. Whether 
by this means or by inflammatory products, they probably have a 
part in the production of gall-stones. 

Among the gastro-intestinal troubles it has been found in suspicious 
abundance in various forms of enteritis, in the distended and suppurat- 
ing appendix, and even in Asiatic cholera. It is known that the strangu- 
lation of a knuckle of intestine by a ligature leads to rapid increase of 
virulence of the contained bacilli. It is possible that in appendicitis 
and in other intestinal diseases similar conditions lead to increased 
infectivity, and thus cause an ordinarily harmless organism to become 



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297 



virulent. In the cases of Asiatic cholera in which this organism has been 
found the specific germ of cholera has probably been overlooked or has 
disappeared during the rapid multiplication of the saprophytic Bacillus 
coli. 

Peritonitis may result from escape of the bacillus through a rup- 
tured intestine or directly through the wall of the bowel. The latter 
is particularly prone to occur in cases of strangulation of the intestines. 

Various inflammatory diseases of the urinary tract, such as cystitis, 
pyelitis, and pyelonephritis, are occasioned by this same germ, which 
first reaches the bladder through the urethra or by penetration of the 
wall of the bowel and then of the bladder, or, in other cases, infects the 
kidney primarily, having been carried there by the blood. 

Finally, there are cases of peritonitis secondary to enteritis, pleurisy, 
endocarditis, and other inflammatory diseases, apparently caused by 
this organism. 

Pathological Physiology. — Little is known of the toxic effects of coli 
infection. Some toxic substance is doubtless produced, which, according 
to Vaughan, is a highly thermostabile intracellular substance. A reac- 
tion similar to the Widal reaction obtained with the typhoid germ has 
been found to occur when cultures of the colon bacillus are subjected to 
the action of serum from an animal inoculated with this organism or 
from a person suffering with appendicitis or other diseases, either due to 
coli infection or accompanied by such. Occasionally the colon bacilli 
agglutinate and their motility is checked by typhoid serum. The ex- 
planation of this may be that in certain cases of typhoid fever the colon 
bacillus is also active in the intestines, and in consequence a mixed form 
of infection is present. In part it is also the result of the presence of 
group agglutinins that act on different but allied organisms. 

There is no antiserum for colon infections, but vaccination treat- 
ment has been used with success. 

THE DYSENTERY BACILLUS 

Certain types of dysentery in the tropics and of acute dysentery 
of temperate climates are accompanied by bacilli, first recognized by 
Shiga, and afterward studied by Flexner, Park, Kruse, and others. 

The organisms resemble those of the typhoid group, except that 
they are questionably motile bacilli with few, if any, flagella. 

In gelatin culture the colonies resemble those of typhoid bacilli. 
In bouillon a diffuse cloudiness without production of indol is observed. 
In glucose bouillon the bacillus does not produce gas or acid. The 
organisms, as observed by different observers, have differed in some 
particulars. The original form recognized by Shiga does not ferment 
mannite, maltose, or saccharose. Some of the later types have been 
found to ferment mannite and to produce indol, while still others 
actively ferment mannite and also maltose and saccharose. 

The bacillus produces a highly toxic poison, probably of both intra- 
and extracellular nature. It is resistant up to 70° C. (158° F.), and to 



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proteolytic ferments. Upon experimental animals the organism has a pre- 
dilection for the colon. An antiserum has been prepared containing both 
antitoxic and bactericidal properties. Agglutinins occur during infection. 

Bacilli almost identical with the true tropical dysentery bacillus have 
been found in the summer diarrheas of children. The cases may occur 
in epidemic or sporadic form. Agglutination tests are used to separate 
them in the same way that the paratyphoids, typhoids, and paracolons 
are separated. 

The pathological anatomy and physiology of dysentery will be con- 
sidered in the section on Diseases of the Intestines. 

INFLUENZA 

Definition. — Influenza is an infectious disease occurring in wide- 
spread epidemics and caused by a specific bacillus. 

Etiology. — The Mycobacterium influenzas was discovered by Pfeiffer 
and Canon in 1892. The bacilli are extremely small and usually occur 
singly, though they are occasionally united by the ends, forming short 
chains. They may be stained with the ordinary anilin dyes, especially 
with carbol-fuchsin, but are decolorized by Gram's method. The ends 
of the bacillus are somewhat swollen and usually stain rather more deeply 
than the shaft. This gives the organism somewhat the appearance of a 
diplococcus or dumbbell-shaped bacillus. It is not motile. The first 
generation of the bacilli will grow only in the presence of hemoglobin 
and are, therefore, cultivated upon glycerin-agar the surface of which 
has been smeared with rabbit or human blood, forming minute dew-drop- 
like colonies, seen with difficulty with the naked eye, but clearly with the 
aid of a lens. The colonies do not coalesce. The appearance of the 
growth is somewhat like that of condensed moisture on the surface of 
the culture-medium. Later generations of bacilli may be cultivated on 
agar or in bouillon. 

The bacilli occur abundantly in the sputum of the disease, decreas- 
ing in quantity as the case advances. When purulent expectoration 
ceases the bacillus disappears entirely. Not rarely the organisms are 
readily recognized in the sputum by simple staining methods. A 
certain diagnosis is not possible in this way and even in cultures other 
organisms (see below) have a puzzling resemblance. In fatal cases it 
has been found in abundance in the tissues of the lung, particularly in 
cases in which complicating pneumonia has existed. Animal experi- 
mentation has thus far been unsatisfactory, though the organism has 
proved pathogenic for rabbits and monkeys. The symptoms are sug- 
gestive of human influenza, but entirely conclusive results have never 
been obtained. The specific character of the organism is, therefore, 
inferred rather than demonstrated. 

Pathological Anatomy. — There are no specific lesions in this dis- 
ease. The organisms provoke intense catarrhal processes and, doubt- 
less at times, pneumonia. In some cases the pneumonia of influenza 
is caused by mixed or secondary infection. Resistant influenzal infec- 



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299 



tions of the bronchial tubes, with bronchiectasis, constitutes a clinical 
type of chronic influenza. Inflammatory lesions and hemorrhagic 
infiltrations in the membranes of the brain and just beneath the mem- 
branes have been observed. 

A true influenzal meningitis is met in children and can be produced 
in monkeys. There is an associated bacteremia. Antibody-containing 
serum can be obtained by injecting the bacilli into goats. This may 
prove of value in influenzal meningitis, as it has a power of stimulating 
phagocytosis in the spinal fluid. Bacterins have been used in the 
treatment of catarrhal influenza. Agglutinins are formed during an 
attack. 

Pathological Physiology. — Very little is known regarding the mode 
of activity of the bacteria. The constitutional symptoms suggest 
toxemia, but the nature of the poison is obscure. The immunity from 
the disease must be exceedingly short, as recurring attacks and relapses 
may be frequent and succeed one another rapidly. It has been found 
that the influenza bacillus may remain in the bronchial tubes, especially 
in tuberculous cases, for months or years. From time to time renewed 
acute infection takes place. Certain complications and sequels, such as 
inflammations of the serous surfaces and neuritis, indicate generalized 
infection and intoxication. The organism does not seem to thrive or 
multiply in the blood. It has been found in otitis media and other con- 
ditions which suggest a metastatic deposit. In general, however, in- 
fluenza seems to be a local infection with general toxemia, but rarely 
general infection. 

Organisms Resembling the Influenza Bacillus. — A very similar 
organism, called the pseudo-influenza bacillus, has been described. It 
is somewhat larger and tends to form long filaments. 

The Koch-Weeks bacillus of epidemic conjunctivitis differs in its 
manner of growth and in the fac{ that hemoglobin is not necessary in 
the media. It is non-pathogenic in animals. Another influenza-like 
organism found in conjunctivitis is the Morax-Axenfeld bacillus (Bacillus 
lacunahis). This is, however, larger and grows only in the presence of 
blood or serum, liquefying the latter. These two organisms seem specific 
for the conjunctiva. 

BORDET-GENGOU BACILLUS OF WHOOPING-COUGH 

This organism is now accepted as constantly present in cases of per- 
tussis. According to the studies of Wright, it lies between the cilia of the 
bronchial epithelia, and so interferes with their movements that violent 
efforts to remove it cause the prolonged coughing attacks. By many 
authorities, notably the discoverers of the germ, it is looked upon as the 
cause of the disease, because they can use cultures of it as antigen and fix 
the complement from the hemolytic series. The organism is a minute 
ovoid, sporeless, non-motile, poorly staining, Gram-negative rod. It 
grows aerobically upon media containing glycerin, potato, blood, and 
agar. The effects are due to an endotoxin. Conditions similar to per- 



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A TEXT-BOOK OF PATHOLOGY 



tussis have been produced in monkeys and dogs by injection and in- 
sufflation of cultures. Agglutinins are said to be formed. Bacterins 
can be used. 

BUBONIC PLAGUE 

Definition. — The bubonic plague, or pest, is an infectious disease 
due to a peculiar bacillus, Bacterium pestis. 

Etiology. — The bacillus of bubonic plague was discovered by 
Yersin in 1894. In blood drawn from a puncture of the skin and in pus 
from the affected glands may be found small bacilli somewhat resem- 
bling the influenza bacillus. These organisms may be stained readily, 
and often more deeply at the poles than in the center (Fig. 108). This 




Fig. 108. — Plague or pest bacilli in smear from spleen. 



gives them an appearance resembling that of the diplococci, and in 
specimens from the blood or tissues there is an indistinct capsule. The 
organism is rather oval in shape, but club-shaped forms are frequent, 
and in cultures long chains are met with. It is not motile; Gram-nega- 
tive; it may live in gelatin between 5° and 20° C. (17° and 68° F.) 
without liquefying the medium. It thrives best in the presence of 
a high degree of moisture. Pure cultures have been obtained upon 
various media. Upon glycerin-agar moist, rounded, whitish, or bluish- 
white colonies are formed. Portions of such colonies removed for 
examination show the bacilli ranged in chains. The growth in bouillon 
is very characteristic, as stalactite formations hanging from the surface 
of the fluid. 

Pathogenicity. — The bacillus has been found pathogenic for mice, 



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301 



rats, guinea-pigs, rabbits, and, indeed, any domestic animal; and the 
symptoms produced by pure cultures are the same as those induced 
by inoculating animals with blood or portions of tissue from diseased 
persons. The lymphatic glands may be swollen and petechial hemor- 
rhage may occur as in the human disease. 

Distribution. — In the human being suffering from bubonic plague 
the bacilli are found in the local lesions of the lymphatic glands, the 
buboes; and also in the blood and various organs. Yersin showed 
that flies die of the disease, and succeeded in obtaining the bacillus from 
their dead bodies. They do not flourish in water, but thrive in milk, 
butter, and cheese, and these food-stuffs may spread the contagion. 
The pneumonic form is usually caused by inhalation of dust that has 
not dried sufficiently long to destroy the bacteria, but is not necessarily 
due to inhalation of the germs in all cases. 

It has been shown that the breath during quiet respiration of plague 
pneumonia patients does not contain germs, but they are expelled by 
coughing. 

The rat and its fleas are the means of propagation of plague. It 
has been said that plague is primarily a disease of rats, and that man is 
only an accidental host. Transmission from animal to animal and 
animal to man takes place by the rat flea, which will bite man. Bacilli, 
existing in the saliva and digestive tract, may easily be deposited upon 
the surface of an animal or man and rubbed into any small wound of 
the skin, such, for instance, as may be made by the flea-bite. Bacilli 
may also be deposited by fleas or rats upon food or household utensils. 

Not only rats but most rodents are susceptible to plague. Ground 
squirrels of California have been found extensively affected, and the 
marmot of Tibet is a constant source of infection in that country. 

It is said that mild, unrecognized cases may act as "carriers." 

Pathological Anatomy. — There are three forms of plague according 
to the chief clinical and anatomical manifestations: the bubonic, pneu- 
monic, and septicemic. The organism produces swelling and suppuration 
of lymphatic glands, particularly those of the groin, and, secondarily, 
lesions of internal organs. The lymphatic glands swell quickly, become 
tender and congested, and then soften, forming a rather thick pus. This 
is sometimes blood tinged. Histologically, the exudate is chiefly large 
mononuclears, actively phagocytic of the very numerous pest bacilli. 
This form of exudate soon gives way to necrosis and spread of bacilli 
outward. Petechial hemorrhages and blood-stained effusions into the 
serous cavities may occur. Petechise of the skin are apt to develop 
as a result of slight traumatisms. Thus, the bite of an insect, instead 
of producing its usual results, may cause distinct ecchymoses in persons 
suffering from the disease. The pulmonary form produces a bloody 
edematous form of pneumonia; fibrin appears relatively late. This 
may be quite independent of glandular enlargements externally. A 
"septicemic form" is characterized by general infection with wide- 
spread involvement of the lymphatic glands, but without distinct 
buboes. Areas of necrosis take the place of pest abscesses. 



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Pathological Physiology. — It seems that the distribution of the 
bacillus in the blood, as well as toxic substances, chiefly endotoxin, 
contribute to the general disturbance of health. By successive inocu- 
lation immunity has been produced, and antitoxic sera have thus been 
obtained. The serum has been used in man with considerable success 
as a protective and also a curative agent. It often fails in advanced 
cases. 

Haffkine used his method of inoculation as in cholera and obtained 
encouraging results. 

SOFT CHANCRE 

Definition. — The soft chancre or chancroid is an infectious venereal 
sore appearing upon the external genitalia. The bacillus of Ducrey is 
said to be the specific organism. 

Etiology. — The soft chancre occurs almost exclusively upon the 
genital organs or the surrounding parts. It is always caused by direct 
contagion. 

The bacillus of Ducrey and Unna is a rod-shaped organism about 
1.8 ^ in length and 0.5 fi in thickness, and appears somewhat com- 
pressed in the middle, so that it has a figure-of-8 shape. The ends are 
rounded and the organisms often occur in chains, or later in the disease 
in pairs, as a diplobacillus. 

The demonstration of the bacillus in the pus is comparatively 
easy. The specimen is stained with alkaline solutions of methylene- 
blue and quickly decolorized with weak acetic acid solution. It may 
be well stained with carbol-fuchsin, alcohol being used to decolorize. 
It is Gram-negative. In the tissues the demonstration is more 
difficult. 

Growth is most luxuriant in a medium of fresh blood and bouillon, 
but unmixed human blood is the best medium for obtaining cultures 
from a source open to contamination, the fresh blood apparently in- 
hibiting to a certain extent the growth of extraneous organisms. The 
best solid medium consists of 2 parts of alkaline agar and 1 part of fresh 
rabbit's blood if seeded with material obtained by aspiration of a bubo. 
Cultures on ordinary media have thus far been unsuccessful. 

The bacillus is found in the pus of the soft chancre, as well as in the 
deeper parts, lying between the cells and frequently within the leuko- 
cytes. It has also been discovered in the pus and walls of ulcerating 
buboes, but is generally absent in the pus of unopened buboes. 

Mixed Infection. — Various other organisms have been found asso- 
ciated with the bacillus, including streptococci, staphylococci, the 
gonococcus, and bacilli of uncertain nature. 

Pathological Anatomy. — The soft chancre is an ulcer of variable 
character. Usually it is a simple ulcer, with suppurating base and edges, 
not differing from ulcers due to other causes. Sometimes the ulcera- 
tion seems more malignant and takes on a phagedenic or serpiginous 
character (see Ulceration). The neighboring lymphatic glands are 
usually enlarged and sometimes undergo suppurative softening (bubo). 



DISEASES DUE TO BACTERIA 



303 



Pathological Physiology.— Little is known of the existence of special 
toxic bodies in this disease. It is believed, however, by some that 
toxins are produced by the bacilli, and that these are capable of pro- 
ducing secondary lesions (bubo) without the presence of the bacilli 
themselves. 

MALTA FEVER 

Synonvms. — Mediterranean Fever; Gibraltar Fever; Febris Undu- 
lans. 

Definition. — This disease has been described as a form of irregular 
fever occurring along the Mediterranean coasts. It was formerly 
regarded as an aberrant form of typhoid fever, but is certainly inde- 
pendent. 

Etiology. — The micro-organism discovered by Bruce, and designated 
Micrococcus melitensis, is by many regarded as the specific cause. This 
is an oval micrococcus about | ^ in diameter, occurring singly or in 
pairs, and in cultures as short chains. By Babes it is regarded as a 
bacillus, and certainly agglutinates with more readiness than cocci are 
wont to do. It has no motility of its own. It may be stained with 
ordinary solutions of anilin dyes, but not by Gram's method. It occurs 
abundantly in the spleen, and is occasionally found in the blood by 
blood-cultures. Pure cultures have been obtained, and inoculation in 
monkeys has seemed to give positive results. Malta fever is not con- 
tagious. The micro-organisms seem to enter the body through the 
respiratory or the intestinal tract. Agglutination occurs readily with 
patients' serum, and may be used in diagnosis. The organism is excreted 
in urine and milk. The goat, which is used largely for milk supply in 
Malta, may carry the germs and excrete them without being actively 
infected with the disease. 

Pathological Anatomy. — The mucous membrane of the small in- 
testine is red and the solitary follicles and Peyer's patches are some- 
times swollen. The mucosa of the large intestine is generally dark red 
and presents small round or larger irregular ulcerations, from which 
intestinal hemorrhages occur. In some cases lesions of the ileum 
resembling those of typhoid fever have been described; but it is doubtful 
if the cases in which these occurred were Malta fever. The spleen is 
enlarged and hyperemic. 

Pathological Physiology. — Malta fever is characterized by irregular 
febrile movements. The cause of this irregularity and the nature of 
the toxic substance generated in the disease are unknown. 

RHINOSCLEROMA 

This is a disease affecting the skin about the anterior nares and 
adjacent parts, and probably caused by a specific bacillus. The dis- 
ease has been especially observed in central Europe. It presents 
itself in the form of nodular thickening of the skin of the nose and lip, 
and sometimes spreads to the neighboring mucous membranes — mouth, 



304 



A TEXT-BOOK OF PATHOLOGY 



pharynx, or larynx. In the latter situations ulceration of the surface 
is frequent; the lesions of the skin rarely ulcerate. Histologically, the 
growth consists of round granulation tissue cells. Frequently the cells 
suffer hyaline degeneration, forming rounded hyaline bodies, with 
small granular nuclear masses. These are called Mikulicz cells. The 
bacilli may be found between the cells and within them, especially such 
as present hyaline degeneration. The micro-organism resembles the ba- 
cillus of Friedlander, but by some is said to be Gram-positive. This is 
denied by others. When cultivated upon blood-serum or agar it retains 
its capsule. Inoculation experiments have thus far failed to produce the 
disease in animals. The etiological relationship of the so-called Bac- 
terium rkinoscleromatis is doubted by many observers. It is very 
close to Friedlander's pneumobacillus, but does not form gas in sugar 
media. 

GLANDERS 

Definition. — Glanders is an infectious and contagious disease of 
horses and asses, sometimes communicated to other animals and to 
man, and caused by a specific bacillus. 

Etiology. — The Mycobacterium mallei was first isolated by Loffler 
and Schiitz. It is an organism resembling the tubercle bacillus, though 
somewhat shorter and thicker. In cultures it may grow to long fila- 
ments and not rarely it breaks up into coccus-like fragments. It occurs 
in the lesions of the disease singly or in clumps, and has been found in 
the blood. The bacillus is non-motile and does not possess flagella. 
Stained specimens show parts that do not receive the stain. These have 
been regarded as spores, but are more generally thought to be areas of 
degeneration. Ordinary solutions of anilin dyes, and especially alkaline 
solutions, stain the organism very well. The demonstration of the 
bacillus in the tissues requires prolonged staining and rapid decoloriza- 
tion. It is Gram-negative. 

Cultivation. — Cultures are best obtained from softened nodules 
of guinea-pigs inoculated with infected pus, or from the testicles after 
injection of infective matter into the peritoneal cavity. The organism 
grows quite readily upon ordinary media, but the most characteristic 
culture is seen upon boiled potato. The colony first appears as a honey- 
like layer, which becomes brownish in color. The potato itself becomes 
greenish brown beneath and around the colony. The cultivation is most 
successful between 30° and 40° C. (86° and 104° F.). 

Drying and elevated temperatures rapidly destroy the organism, 
and germicides kill it quite readily. The bacillus is a pure parasite, 
multiplying only in the body of infected animals or man. 

Pathogenicity. — The specific character of the bacillus is unques- 
tionable. Inoculation of guinea-pigs, rabbits, field-mice, or other ani- 
mals with infected pus or with pure cultures leads to nodular lesions at 
the point of introduction, with subsequent softening and ulceration. 
Secondarily, the lymphatic glands enlarge and after from two to four 
weeks suppurate. In male guinea-pigs a practically pathognomonic 



DISEASES DUE TO BACTERIA 



305 



condition (great enlargement of the testicles) is observed within two 
or three days after intraperitoneal inoculation with pure cultures or 
exudate from the lesions of the disease. After death nodules are found 
in the liver, spleen, kidneys, or other organs, and these contain the 
bacilli. In horses and asses characteristic lesions of the mucous mem- 
branes have been produced experimentally; while in man accidental 
infection of hostlers or others coming in contact with diseased animals, 
and of bacteriologists working with cultures, have been repeatedly 
observed. In one case in our own knowledge a man was infected in a 
stable in which a glandered horse was kept, and the bacteriologist who 
isolated the organisms from the patient accidentally infected himself 
with the cultures. The spontaneous infection occurs through some 
abrasion or wound. 

There are two fairly distinct forms of glanders, the acute and chronic. 
The former is septicemic with abscesses, both widely scattered in the 
organs and in the lymphatics of the skin (farcy buds) . The term farcy 
is given to the form with subcutaneous abscesses, usually an acute 
condition in man, but commonly more chronic in horses. The chronic 
form is slow of progression, chiefly attacking the lymphatic organs, 
and showing slowly progressive lesions either local or general. 

Pathological Anatomy. — In horses glanders presents characteristic 
lesions of the mucosa of the nose. At first there are found slightly ele- 
vated nodules, which have a marked tendency to soften, forming irreg- 
ular ulcerations that become confluent. The floor and edges of the 
ulcers are yellowish and necrotic in appearance, and discharge more or 
less purulent matter. The lymphatic glands of the neck and elsewhere 
enlarge and may suppurate. In the skin the lesions are much the same, 
but more sluggish. Nodules are not rarely met with in the lungs. 
These are grayish or pinkish in color, and tend to rapid necrosis. More 
rarely nodules or ulcers are found in the mucosa of the gastro-intestinal 
tract. 

In man similar nodules and ulcerations may be found in the nose, 
larynx, or trachea; and external lesions resembling small or large car- 
buncles are found. 

Histologically, the lesions of glanders consist of aggregations of 
round cells of lymphoid or polymorphonuclear type surrounded by a 
zone of spindle and epithelioid cells. Some of the latter swell, and their 
nucleus divides by direct division, causing a kind of giant cell. There is 
a marked tendency to suppurative or necrotic softening, and some- 
times hemorrhagic infiltration may be pronounced. 

Pathological Physiology. — A toxic substance called mallein (a bac- 
terial protein) has been obtained from cultures of the bacilli. Injected 
into infected animals this acts somewhat as does tuberculin in tubercu- 
losis. A special toxin is probably active in the production of the general 
symptoms of the disease. By repeated dosage with mallein it is claimed 
that immunity may be conferred. The poison of Mycobacterium mallei 
is endotoxic. Agglutinins are produced during an attack, and a com- 
plement-fixing body can be discovered in most cases. 
20 



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TETANUS 

Definition. — Tetanus is an acute infectious disease due to a specific 
bacillus, the Bacillus tetani, discovered by Nicolaier and isolated by 
Kitasato. 

Etiology. — The bacilli occur in the form of cylindrical rods, which 
are frequently swollen at one end, due to the presence of a rounded 
spore (Fig. 109). They are slightly motile in the vegetative state, being 
supplied with peritrichous flagella; in the spore stage they are non- 
motile. They usually occur singly, though occasionally a few may be 
seen end to end. They occur in the local lesions from which traumatic 
tetanus takes its origin, and may sometimes be readily demonstrated 
by spreading some of the pus or exudate upon a cover-glass and staining 
with the ordinary anilin stains. They also stain by Gram's method. 
The bacillus does not diffuse itself through the body, but in a few cases 




Fig. 109.— Bacillus tetani; X 1000 (Frankel and Pfeiffer). 

it has been found in the central nervous system. The organism is read- 
ily destroyed by heat, but its spores are quite resistant. 

Cultivation of the tetanus bacillus is difficult. It is obtained from 
garden-earth or the pus of infected wounds by submitting the material 
to sufficient heat to destroy other organisms, even the bacillus of tetanus 
itself, leaving the spores uninjured. With this material animals are 
inoculated, and from the products of the local lesions or directly from the 
original material cultures are made in gelatin. 

The organism is strictly anaerobic. The typical culture is obtained 
in the depth of gelatin. Deep beneath the surface there are formed along 
the line of puncture pointed processes standing out at right angles from 
the puncture. After a week liquefaction of the gelatin occurs, and an 
accumulation containing grayish-white turbid liquid is formed. When 
the growth is formed on the surface of gelatin in an atmosphere of 
hydrogen a similar radiating structure is found in the colonies, the cen- 



DISEASES DUE TO BACTERIA 



307 



ters of which are rather dense. Liquefaction of the gelatin subsequently 
takes place. Considerable gas with a pungent odor is produced in the 
growth of this bacillus. 

Distribution. — The tetanus bacillus is found very frequently in 
garden-earth, in the intestinal discharges of animals, and upon various 
articles about stables. Infection occurs in human beings or animals 
through punctures made by nails, splinters, and the like. 

Pathogenicity. — The bacillus placed upon an open wound may not 
give rise to the disease, from the fact that the presence of oxygen pre- 
vents its growth. Subcutaneous inoculation, however, causes rapid 
destruction of animals with typical symptoms. The period of incuba- 
tion may be only a few hours, or one or two days, or it may be several 
weeks. The association of certain other organisms, such as the pus- 
producing organisms, seems to favor the development of the disease by 
preventing phagocytic action of leukocytes, or by consuming oxygen 
and thus allowing the tetanus bacillus to flourish. 

The toxin is manufactured in loco and taken up by the nervous 
tissue, for which it has a predilection. 

Pathological Anatomy. — No characteristic lesions are found in this 
disease. Locally, a wound or injury through which inoculation has 
taken place may be discovered ; but this is only exceptionally extensive. 
Sometimes no local injury can be discovered, and it is supposed that in- 
fection at times occurs through the gastro-intestinal tract or through 
other mucous membranes. Intense congestion of parts of the nervous 
system and granular degeneration of the anterior spinal motor cells may 
be found at the autopsy, but these are not characteristic. 

Pathological Physiology. — Two distinct toxins have been recog- 
nized — tetanospasmin, which is the predominant poison and that which 
causes the spasms, and tetanolysin, a hemolytic substance of uncertain 
importance. The toxin of tetanus is almost inconceivably poisonous, 
a fact which accounts for the development of a fatal disease in cases in 
which the number of bacilli is minimal. 

The spasmodic seizures first affect the muscles near the point of 
inoculation and in mild infections may be confined to these muscles. 
This has been explained by the experiments of Meyer and Ransom and 
others, who showed that the toxin reaches the nerve-cells of the spinal 
cord by traveling from the muscular end-plates of the motor nerves 
through the axis-cylinders to the cord. The toxin injected into the 
blood does not pass directly to the nerve-centers, but always travels up 
the motor nerves as described. The parts first affected by spasm are, 
therefore, those about the point of inoculation and of elaboration of the 
toxin. 

Tetanus antitoxin has been obtained by successive inoculations of 
animals with the toxin, and in laboratory experiments has been found 
specific and exact .in its antagonism to the toxin. In treating the dis- 
ease in man or animals the results have been disappointing, but this is 
now known to be due to the manner in which the toxin and antitoxin 
are respectively distributed and absorbed, and to the fact that the toxin 



308 



A TEXT-BOOK OF PATHOLOGY 



has usually reached the vulnerable nerve-centers, and been tightly 
anchored in them, at the time when the antitoxin is injected. The 
antitoxin must be first absorbed by the lymphatics and carried to the 
blood, with which it is distributed to the fluids of the body, whence it is 
again absorbed by the nerves. It is not taken up directly from the 
blood by either the central or peripheral nervous tissue. For these 
reasons the subcutaneous injection of antitoxin fails to effect the neu- 
tralization of much of the toxin, since the latter is quickly absorbed by 
the peripheral nerves. Intravenous, intraneural, and subdural (spinal) 
injections are more rapid in their effects and, therefore, preferred. 
To prevent combination of toxin and nervous tissue antitoxin must be 
introduced before symptoms arise. It is, therefore, more useful as a pre- 
ventive than as a curative. 



Definition. — Anthrax is a specific infection due to a characteristic 
bacillus. It occurs most frequently in cows and sheep; it may affect 
other animals and man. Dogs, cats, birds, and cold-blooded animals 
are quite immune. In animals it is called splenic fever; in man, malig- 
nant pustule and wool-sorters' disease. 



Fig. 110. — Bacterium anthracis, stained to show the spores (Frankel and Pfeiffer). 

Etiology. — The Bacterium anthracis was first observed by Pollender 
in 1849, and shown to be the specific cause of anthrax by Davaine in 
1863. In 1879 Koch, Pasteur, and others succeeded in making pure 
cultures and in demonstrating their pathogenicity. It was, therefore, 
the first pathogenic organism definitely isolated. The anthrax bacillus 
is a non-motile rod-shaped organism that has a decided tendency to form 
long chains. The individual bacillus is from 5 to 20 y. in length and from 
1 to 1.25 u in thickness. The chains appear as threads often with a little 
thickening at the ends of the individual bacilli showing the points of 
contact. The ends are squared or slightly concave. In artificial cul- 



ANTHRAX 




DISEASES DI E TO BACTERIA 



309 



tares in the presence of oxygen spores are formed within the bacilli. 
These are elliptical or oval in shape, and do not alter the configuration 
of the bacillus (Fig. 110). 

The organism is easily stained with the simple anilin dyes, and may 
be demonstrated in the blood or the tissues by Gram's or Weigert's 
stains. There are no flagella. 

Cultivation. — The anthrax bacillus may be obtained in pure culture 
from the diseased organs upon various media. The culture in gelatin 
is most characteristic. Upon plates there are formed whitish colonies, 
which under low powers of the microscope show a tufted, irregular 
character at the edges and upon the surface, suggesting bunches of 
twisted wool-fibers. The gelatin is slightly liquefied. The tufts may be 
removed by pressing a cover-glass against the surface of the colony, and 
when stained are found to consist of curved parallel chains of bacilli. 
In puncture-cultures filaments project at right angles to the puncture 
toward the sides of the test-tube, and the growth at the surface, where 
oxygen is abundant, is luxuriant, while that in the depth is compara- 
tively sparse. 

Pathogenicity. — The infectiveness of the bacillus is undoubted. 
A small portion introduced into a susceptible animal gives rise to 
marked symptoms in twelve or twenty-four hours, and death soon 
follows. The bacilli may be demonstrated in the blood and in various 
organs in great abundance. When the bacillus is killed and the spores 
are introduced into the body similar results follow. The spores are highly 
resistant and may preserve their virulence for years. Sporeless varie- 
ties of anthrax bacilli have been encountered and have been produced 
by cultivation under unfavorable conditions. 

Distribution. — The anthrax bacillus occurs in all of the local lesions, 
and from these is carried into the blood and the organs, particularly 
the spleen, liver, kidneys, and lungs, where it is found in the capillaries 
in immense numbers. The structure of these organs is, as a rule, little 
affected, probably because death occurs before changes can take place. 
The organisms may be present in only small numbers in the blood of the 
general circulation when the capillaries of the various organs are filled 
with them. The organisms are discharged from the body in the stools, 
urine, and other discharges, and are thus conveyed to other animals. 
At one time it was supposed that they were scattered about by earth- 
worms obtaining them from cadavers; this is scarcely probable. Mul- 
tiplication of the organisms outside the body does not occur to any 
extent, but the organisms, and particularly the spores, may live a long 
time, and may be conveyed to great distances in infected materials, 
particularly wool, hides, bristles, and the like. 

Mode of Infection. — In animals infection most frequently occurs 
through the gastro-intestinal tract, the bacilli being swallowed with 
fodder that has been contaminated. The organisms may, however, 
gain entrance through the lungs or through external abrasions. The 
latter form of infection is most common in man, though gastro-intestinal 
and pulmonary infection sometimes occur. 



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A TEXT-BOOK OF PATHOLOGY 



Pathological Anatomy. — The lesions produced by anthrax are more 
or less local, but occasionally are septicemic. In man, after infection 
of the skin through abrasions in persons handling the hides or wool or 
other materials from diseased animals, a swelling of greater or less size 
develops. This is intensely inflammatory, often covered and surrounded 
by slight bullous vesicles, and attended with considerable edema. Ero- 
sion of the surface may take place and sanious liquid may be discharged, 
with the formation of crusts. Histologically, the process consists of 
rapid infiltration of the corium and papillary bodies with leukocytes. 
The bacilli are found in abundance between the cells, and hemorrhagic 
infiltration and serosanguinolent edema are observed. Necrosis sub- 
sequently occurs, though not to a considerable extent. When infection 
takes place through the gastro-intestinal tract, as is sometimes ob- 
served in man and very commonly in animals, lesions somewhat like the 
above are formed in the mucosa and submucosa of the small intestine, 
less frequently of other parts. At first these lesions appear as hemor- 
rhagic extravasations, then swelling follows, and finally the surface 
ulcerates, leaving irregular excavations with blood-stained bases and 
edges. Profuse diarrhea with bloody discharges may occur. Infection 
through the lungs occurs in men engaged in handling infected wool 
(wool-sorters' disease), and in persons working in paper factories, where 
infected rags carry the germs. In these instances the bacilli lodge in the 
alveoli of the lungs, causing rapid cellular exudation with considerable 
edema and hemorrhagic infiltration. The process is lobular in charac- 
ter, but large areas of the lungs may be simultaneously involved. Sero- 
sanguinolent pleurisy, swelling of the lymphatic glands of the medias- 
tinum, and hemorrhagic extravasations of the mediastinum are not 
unusual. In all forms there is acute inflammatory or hemorrhagic 
swelling of the spleen. 

Pathological Physiology. — The presence of the anthrax bacillus 
probably leads to the formation of toxic materials in the blood, although 
while a poisonous albumose has been obtained from cultures, its nature 
is not understood and its identity doubted by some. The general 
symptoms, however, are probably in large measure the result of dis- 
semination of the bacilli themselves and their local effects. 

Their action seems to be directed primarily against the circulatory 
system, as the toxin calls forth leakage of serum and escape of blood. 
Much fibrin is formed, but there is little tendency to cellular accumula- 
tion or suppuration. 

It has been found possible by cultivation at high temperatures, 
by introducing the organisms into insusceptible animals, and also by 
adding chemical agents to cultures to alter the pathogenicity of the 
bacillus to such an extent as to make it harmless, even to white mice. 
By introduction of such cultures and subsequent successive inoculation 
with cultures of increasing virulence protection has been afforded. 
Antitoxic substances have been obtained from the blood of protected 
animals, but the method of successive vaccinations rather than the use 
of antitoxic serum is at present relied upon to combat the disease. 



DISEASES DUE TO BACTERIA 



311 



MALIGNANT EDEMA 



Definition. — Malignant edema is a form of intense infective in- 
flammation and necrosis observed in certain animals and in man, and 
is due to a specific micro-organism. The condition has frequently 
been described by clinicians as gaseous gangrene, traumatic gangrene, 
gangrene foudroyante, etc. Infectious emphysema (q. v.) has doubt- 
less often been mistaken for this disease. 

Etiology. — The micro-organism of malignant edema 
was described by Pasteur and named the Vibrion sep- 
tique. Koch showed that it does not flourish in the 
blood, and that the name given by Pasteur is, there- 
fore, not appropriate. He, therefore, named it Bacillus 
cedematis maligni. This organism is widely distributed. 
It is very commonly present in the soil, particularly in 
garden-earth, and is often found in dust and in the 
intestinal contents of animals. Introduced into the 
subcutaneous tissue of animals it multiplies greatly and 
sets up a violent local process. The bacilli are readily 
obtained from the diseased area, and may be stained 
with the ordinary anilin dyes, but not by Gram's 
method. The bacillus resembles the anthrax bacillus 
very closely, but is somewhat more slender. It is prone 
to occur in pairs or in chains or long filaments, the 
several bacilli being joined end to end. Movement of 
the organisms is frequently observed, and lateral flagella 
are found by appropriate stains. In the spore forma- 
tion the center of the organism swells and the spore 
is developed within. 

The cultivation of this organism is generally easy. 
White mice or other susceptible animals are first 
infected by introducing powdered garden-earth into 
a subcutaneous sac. Direct infection of an open 
wound will not succeed, as the organism is strictly an- 
aerobic. 

From the pus in the subcutaneous tissues growths may be obtained 
upon the surface of gelatin in an atmosphere of hydrogen, or in puncture- 
cultures in gelatin from which oxygen has been excluded. On the 
surface of the gelatin are formed small grayish-white bodies, which in- 
crease in size with advancing age. Portions removed from these and 
stained show masses of bacilli in the form of long filaments. In the 
gelatin-tube there are formed whitish spherical colonies of a somewhat 
cloudy appearance. These consist of a turbid liquid, the gelatin under- 
going liquefaction. There is also some gas production, the gas formed 
having a peculiar and unpleasant odor. This is marked when the medium 
contains glucose (Fig. 111). 

Distribution. — The bacillus of malignant edema occurs only in the 
subcutaneous tissues near the point of inoculation, in the muscles, and 



Fig. 111.— Ba- 
cillus of malig- 
nant edema grow- 
ing in glucose- 
gelatin (Frankel 
and Pfeiffer). 



312 



A TEXT-BOOK OF PATHOLOGY 



in the peritoneal cavity at the time of death. It does not invade the 
blood, as the amount of oxygen there present prevents its growth, and 
it flourishes in the subcutaneous tissue because this is least accessible 
to oxygen. In bodies dead some time the organism may spread to the 
blood and the organs of the body. The distribution of the organisms 
outside the body has been referred to. 

Pathogenicity. — The bacillus of malignant edema is undoubtedly 
the cause of the disease in question, as has been proved by inocula- 
tions upon mice, guinea-pigs, and other animals. Cats and dogs are 
less susceptible than other animals; cattle seem to be almost wholly 
immune. 

Pathological Anatomy. — The lesions of malignant edema consist of 
various forms of rapid suppuration and necrotic inflammation of the 
subcutaneous tissues. These may rapidly form emphysematous and 
gangrenous alterations of the subcutaneous tissues, with sometimes 
pus formation, at other times extensive hemorrhagic infiltration. 

Pathological Physiology. — Toxins are doubtless formed, but these 
have not as yet received special attention. Artificial immunity has been 
secured by injections of sterilized cultures of the bacillus in bouillon, 
and by other methods. A few cases of malignant edema have been re- 
ported in man, some following injection of musk in the course of typhoid 
fever, some occurring in the puerperium, and some apparently without 
external injury. Infection in the latter probably occurred from the 
mucous surfaces. In all cases the general vitality of the patient was 
reduced by some previous disease. 

INFECTIOUS EMPHYSEMA 

Definition. — This term is provisionally applied to a form of infec- 
tion that has been described under various names, such as gaseous 
gangrene, gas phlegmon, emphysematous necrosis, and the like. Un- 
doubtedly it has been mistaken for malignant edema in certain cases. 
The disease is caused by the Bacillus aerogenes capsulatus of Welch and 
Nuttall. 

Etiology. — The bacillus in question is a non-motile organism of 
variable size, 3 to 6 in length, and about the thickness of an anthrax 
bacillus, with adjacent ends slightly rounded or square cut, and occur- 
ring singly, in pairs, clumps, or sometimes in short chains. Very rarely 
it occurs in long threads. It is easily stained with the ordinary anilin 
dyes or Gram's stain. A capsule is sometimes demonstrable in specimens 
obtained from the body or from agar-cultures. The bacillus does not 
form spores. It is probably identical with the Bacillus phlegmones 
emphysematosa of Frankel. 

Cultivation. — The organism is anaerobic, no growth occurring on 
the surface of solid media in the presence of oxygen. In media contain- 
ing fermentable material gas formation is regularly observed. The 
colonies in agar are grayish-white or slightly brownish; those in the 
depth appearing as small spheres or ovals slightly flattened, with knob- 



DISEASES DUE TO BACTERIA 



313 



like or feathery projections. The cultures in gelatin show slight and 
slowly developing liquefaction. 

Pathogenicity. — By experiments on animals exactly the same lesions 
are produced as those found in man. 

Pathological Anatomy. — The lesions of this infection are wide- 
spread. At the point of inoculation there may be found edematous in- 
filtration, with blood-stained fluid, and emphysema due to gas formation. 
Rapid necrosis or gangrenous softening of the tissue may occur. The 
entire surface of the body sometimes becomes emphysematous, and 
at the autopsy the organs, especially the myocardium, kidneys, liver, 
and spleen, present a characteristic appearance. They are lighter in 
color, and on inspection are found to be filled with minute vacuoles or 
gas-bubbles. The blood of the heart and vessels presents a foamy 
condition, due to the gas formation. Practically, any of the tissues of 
the body may be affected. Microscopically, the occurrence of gas- 
vesicles with numerous bacilli in their walls is the most striking feature. 

Regarding the mode of infection, it seems likely that in all cases 
the organisms enter through some injury or abrasion connected with the 
external world. Some cases have followed traumatic injuries, others 
occur in connection with disease marked by ulcerations of the surface 
of mucous membranes, and at least one instance has been carefully 
studied in which the disease occurred during the puerperium, probably 
due to uterine infection. It is not improbable that some of the cases 
of supposed air-embolism from douching of the uterus after labor are, in 
reality, cases of this form of infection. 

Other bacteria, notably Bacterium mucosus capsulatus, B. coli, and 
B. perfringens, have been found in gaseous edema, or as gas producers 
in inflammatory exudates. 

TUBERCULOSIS 

Definition. — The term "tuberculosis" refers to various condi- 
tions due to infection with the tubercle bacillus, Mycobacterium tubercu- 
losis, no matter what the form or individual peculiarities of the case. 
The name was originally employed because of the occurrence of small 
nodules or "tubercles." It must be remembered, however, that other 
diseases show small miliary nodules, perhaps indistinguishable to the 
naked eye from miliary tubercles, and that tuberculosis sometimes 
occurs without a single definite tubercle. 1 

Etiology. — Tuberculosis is infectious and contagious, the bacilli 
being transferred by the secretions and excretions from diseased per- 
sons to a susceptible individual through the air, food, drink, or in 
other ways. The infectious character of the disease was long suspected, 
but was definitely proved by Villemin in 1865, and in 1882 Koch suc- 
ceeded in isolating the infective bacillus. Predisposing causes are of 
some importance. Formerly family susceptibility was thought an all- 

1 In this book the adjective "tuberculous" applies to the specific disease caused by 
the bacillus of Koch, other conditions being called "tubercular." 



314 



A TEXT-BOOK OF PATHOLOGY 



important cause, and the disease was supposed to be transmitted 
directly in families. At the present time we recognize the transmission 
of susceptibility, and very rarely transmission of the disease itself, from 
parent to child. Warthin has found many cases in literature and his 
own observation where direct transplacental passage of tubercle bacilli 
has occurred, both with or without lesions in the placenta. Tubercle 
bacilli have been found in the semen. (See Placenta.) Susceptible 
persons frequently show delicate organization with poor development 
of the body, particularly of the chest. When this susceptibility or pre- 
disposition exists, there is naturally greater receptivity for bacilli 
spread around by tuberculous associates. Besides inherited suscepti- 
bility, acquired predisposition 
may result from occupations 
which lower vitality, from grief, 
prolonged nervous strain, and ex- 
haustion; and some one of the 
organs may be specially predis- 
v_ posed by injuries, as in cases of 
tuberculosis occurring in the lungs 
of those inhaling sharp particles 
of metal, coal, and the like. Such 
mechanical lesions prepare a place 
of lesser resistance, and tubercle 
bacilli more easily gain a footing 

Fig. 112.— Tubercle bacilli in the sputum; xL • nnrrna l ti«np« Tnn 
Zeiss's homog. immersion Oc. 4; magni- tnan ln normal USSUes. con- 
ned about iooo diam. tinued local anemia seems to 

predispose. 

The human tubercle bacillus is a rod-shaped organism, 1.5 to 3.5 ft 
in length and from 0.2 to 0.5 (J. in breadth. Sometimes it is even longer, 
especially after cultivation. It often occurs in pairs or in groups arranged 
end to end, but not overlapping, and evidently not attached the one 
to the other. It also occurs either straight or more or less curved, and 
may often be found S-shaped or in branching forms. When stained, it 
may either appear uniformly colored or may present a beaded appear- 
ance, regarded by some as due to spores, a view that has not been proved. 
The condition is caused by the alternation of portions well stained 
and intervening parts with little or no stain (Fig. 112). These light 
areas, formerly regarded as spores (Koch), are now believed to be 
the result of fragmentation of the bacillus and retraction of the sub- 
stance of the organism causing vacant areas. In other words, the light 
areas are due to degeneration. They are certainly not spores. There 
appears to be a narrow capsule closely applied to the organism, and the 
capsule seems to contain in especial abundance the wax-like substance 
that occasions the peculiar acid-fast staining properties of the bacillus. 
The bacillus is non-motile and does not have flagella. It is, therefore, 
transported by outside agencies entirely. 

The tubercle bacilli found in man, cattle, and fowl exhibit struc- 
tural and cultural differences, though they are probably the same 



DISEASES DUE TO BACTERIA 



315 



bacilli exhibiting different characteristics caused by their growth in 
different environments. 

The bovine bacillus is much shorter and thicker than the human 
bacillus, being from 1.5 to 2 in length and of an oval shape, the length 
being not more than double the breadth. It is straight, and does not 
exhibit the curved and branching forms of the human bacilli. When 
stained, it is more uniformly colored, the beading being usually absent. 
Cultures of the bovine organism in glycerin broth are at first acid, but 
become alkaline, while those of the human species never become alkaline. 

Tuberculin made from the bovine species is 
alkaline; that from the human species is 
highly acid. 

The human type is more easily grown. 
The bovine type will infect rabbits uniformly, 
while great quantities of human culture are 
necessary. Human bacilli will not infect 
calves with progressive lesions. 



fa 




Fig. 113. — Culture of tubercle Fig. 114. — Bacillus tuberculosis; adhesive cover- 

bacilli on glycerin-agar, four weeks glass preparation from a fourteen-day-old blood- 
old (Friinkel and Pfeiffer). serum culture; X 100 (Frankel and Pfeiffer). 

The avian tubercle bacillus differs from the human bacillus in that 
it is more often club shaped and branching, and that it grows more 
luxuriantly upon glycerin-agar and blood-serum, and at a much higher 
temperature — 45° C. (113° F.). It will also grow on ordinary agar, 
but not on potato. It is much more resistant to heat, especially as re- 
gards its virulence. It will not infect guinea-pigs with a progressive 
lesion. 

Artificial culture of the Mycobacterium tuberculosis was first success- 
fully accomplished by the use of blood-serum as a medium. The bacillus 
grows very slowly; after ten days or two weeks the surface of the medium 
shows dry flakish deposits, somewhat resembling the scales in certain 



316 



A TEXT-BOOK OF PATHOLOGY 



skin diseases (Fig. 113). The edges of these flakes tend to elevate them- 
selves a little, and the substance of the growth has a crumbled appear- 
ance. Placed under a cover-glass in mass and examined with the 
microscope these flakes are found to be composed of contorted masses 
of bacilli (Fig. 114). Pure cultures are best obtained from the lymphatic 
glands of animals artificially infected and destroyed before the tuber- 
culous foci have advanced to the stage of necrotic change. Cultures 
may be obtained with some difficulty from the sputum or other excreta. 
At the present time blood-serum is less frequently used, as it has been 
found that agar-agar slightly acidulated and containing a large pro- 
portion of glycerin, and bouillon containing glycerin, serve as useful 
media. The original culture is still, as a rule, obtained in blood-serum 
or coagulated egg. Even potato and other simple substances are found 
to be satisfactory media. The bacillus requires a rather even tempera- 
ture for its growth: it flourishes best at 37.5° C. (99.5° F.), and does not 
grow below 29° C. (84° F.) or above 42° C. (107.6° F.). Exposure to 
higher temperatures (75° C; 167° F.) rapidly destroys it, and strong 
sunlight is destructive. It requires considerable air and always grows 
upon the surface of the medium in which it is cultivated. Prolonged 
cultivation upon artificial media lessens its virulence. 

The demonstration of the tubercle bacillus by staining methods is 
extremely easy and satisfactory. It has been found that this organism, 
like that of lepra and the smegma bacillus, does not readily stain, but 
after receiving a stain retains it despite the action of strong mineral 
acids. Upon this principle the methods of staining are based. Koch 
used as a stain a gentian-violet solution containing anilin oil, the latter 
playing the part of a mordant or an agent to fix the stain in resistant 
bacilli. The specimen was then decolorized by treating it with a solu- 
tion of a mineral acid, which removes the stain from everything but the 
tubercle bacillus. A counterstain might then be used to render the de- 
tection of the bacilli more easy. 

The most convenient method is the following: Sputum is spread 
in a film upon thin cover-glasses or slides. These are allowed to dry in 
air and then thoroughly fixed by drawing the specimen through a 
Bunsen flame three times; a drop or two of Ziehl's solution of carbol- 
fuchsin are added and heated until the liquid steams. After two or three 
minutes the stain is washed off with water and a few drops of Gabbett's 
solution (methylene-blue, 2; sulphuric acid, 25; water, 75) are placed upon 
i't and allowed to remain a minute or two. The specimen is again 
washed with water, and should then be uniformly blue; if not, a little 
more Gabbett's solution is added as before. In this method the carbol- 
fuchsin stains everything, including the tubercle bacillus; the sulphuric 
acid of the second solution decolorizes everything but the tubercle 
bacillus; and the methylene-blue at once stains the cells and other 
elements, leaving the bacilli dark red. Even more satisfactory results 
may be obtained by allowing the carbol-fuchsin to stain at ordinary 
temperatures for twelve hours; and in the staining of bacilli in tissues 
this prolonged cold staining is particularly desirable. Gram's method 



DISEASES DUE TO BACTERIA 



317 



gives positive results. Pappenheim's solution or repeated treatments 
with absolute alcohol are necessary when it is desired to exclude 
smegma bacilli. 

Distribution of the Tubercle Bacillus. — This organism is probably 
a pure parasite, occurring and multiplying only in the body or excreta of 
diseased individuals, human or animal. Sputa or other excreta contain- 
ing the bacillus may dry and retain the bacillus in a dormant though still 
potential form for long periods of time, outside the body. Multiplication 
of the organism, however, probably very rarely occurs, except within 
the body. The bacillus is found in the lesions of all parts of the body. 

Modes of Infection. — The bacillus may gain access to the body either 
by direct inoculation, by the inhalation or swallowing of the germs, or 
by intra-uterine transference through the placenta. Direct inoculation 
through external wounds is perhaps more frequent than is believed. 
Definite lesions of the skin have been caused by vaccination, and are 
not infrequent upon the hands of anatomists in the form of the so-called 
anatomical tubercles. In some of the cases of scrofulous glands of the 
neck in children it is likely that the bacillus gains entrance through 
abrasions of the skin or of the mucous membrane of the mouth or 
pharynx. Genital tuberculosis is quite possibly frequently produced 
by direct implantation. The most common form of infection is through 
the inspired air. The breath of phthisical patients does not ordinarily 
contain bacilli, but the dust of rooms in which tuberculous patients have 
lived may contain numerous bacilli in a dry state, and these readily be- 
come mixed with the air and are thus inhaled. Tuberculosis of the 
lungs or, more rarely, of other parts of the respiratory tract is thus 
produced in susceptible persons. Despite the activity of some in- 
vestigators to inculpate the intestinal tract in the origin of all lung 
lesions, it is now generally accepted that most pulmonary tuberculosis 
arises by inhalation. The bacilli lodge upon the mucosa, are taken into 
it, or by lymph-radicals, and carried to nearby lymph-nodes. Occa- 
sionally they reach the smaller bronchi and start the lesion there. 
The swallowing of tuberculous material may lead to tuberculosis of 
any part of the gastro-intestinal tract by the direct inoculation that 
results. Thus intestinal tuberculosis in particular is produced. Some- 
times, however, the bacilli pass through the wall of the intestine and 
cause a primary lesion in the lymphatic glands of the abdomen, and it is 
not improbable that even the mesenteric lymphatic glands may escape 
without discoverable lesion or wholly, and the final lodgment of the 
infecting organism may be the lungs. The bacilli are swallowed with 
milk or meat, or they may gain access to the mouth, in the form of dust 
or particles of various kinds, and be swallowed with the saliva. Some 
assert that tuberculosis of the tonsil is of alimentary origin. 

The milk and meat of infected cattle frequently contain bacilli, 
and undoubted instances of infection in this way have occurred. The 
proof of this is that in some cases of abdominal tuberculosis in young 
children the organisms obtained in cultures have shown the character- 
istics of the bovine species. 



318 



A TEXT-BOOK OF PATHOLOGY 



The intra-uterine transmission of tuberculosis is rare, but does occur. 
Most of the cases, however, of tuberculosis in early life may be ex- 
plained as postnatal infections through milk, inspired air, etc. Some 
authorities assume that a few tubercle bacilli transferred from the 
mother to the fetus may lie dormant in the fetus and child and 
later cause active infection. This hypothesis rests upon no demon- 
strated facts. 

Relation of Human to Animal Tuberculosis. — Tuberculosis attacks 
the lower animals with varying frequency. It is most common in 
cattle, and because of the peculiarities of the bacilli and lesions this 
form of the disease is termed "bovine tuberculosis." Many experi- 
ments have been made to establish the relation existing between the 
bovine and human forms of the disease, and Koch, in 1901, made the 
statement that the two were different diseases and probably were not 
intercommunicable. Ravenel disproved this assertion by producing 
the disease in cattle with bacilli obtained from human sources, although 
the animals exhibited a high grade of resistance to such an infection. 
At the same time he reported 4 cases of accidental local infection in 
man with the bovine bacillus. He, therefore, maintains "that human 
and bovine tuberculosis are but slightly different manifestations of one 
and the same disease, and that they are intercommunicable." 

The present situation of the subject is best illustrated by the results 
of Park and Krumwiede. After exhaustive studies of the literature and 
their own material, these authors conclude that while bovine infection 
for the adult is practically negligible, in children a noteworthy per- 
centage of tuberculosis of glands, abdominal organs, and meninges is 
due to the bovine tubercle bacillus. There is no positive proof now at 
hand to show a mutation from one type to the other. 

Less frequently tuberculosis occurs in hogs, goats, horses, dogs, cats, 
sheep, rats, guinea-pigs, and rabbits. All these animals are more 
susceptible when kept in confinement. Captive monkeys are highly 
susceptible. In all these animals the disease is probably intercom- 
municable with human tuberculosis, but the lesions are not always 
identical with those found in the latter disease. Birds and fowl of 
various kinds are susceptible, though the disease is somewhat different 
in them from that seen in man. (See Fowl-tuberculosis.) Tubercu- 
losis of cold-blooded animals has also been recognized. The form of 
disease in the latter is atypical, and the bacillus shows peculiar char- 
acteristics, but tends to approach the form of the human bacillus by 
successive passage through animals. 

Animals may become infected from man, and may further spread 
the infection by their discharges and excretions. In the case of cattle 
the danger of dissemination is particularly great, because of the danger 
to man of infection through the digestive tract by means of tuberculous 
milk or meat insufficiently cooked. 

According to the best testimony available at the present time it 
seems likely that the human, bovine, avian, and other animal species 
are simply variations of one common bacterial organism. Not im- 



DISEASES DUE TO BACTERIA 



319 



probably the peculiar characteristics may be acquired in the human 
body or the animal after the original infection. Thus the proof of the 
original source of the infection may be lost. 

Pathological Anatomy. — Tuberculosis is characterized by the erup- 
tion of small nodules, varying in size from 1 to 2 mm. in diameter to 
that of a small pea. These are known as miliary tubercles. As already 
mentioned, the latter in gross appearance are not distinctive of tuber- 
culosis, as similar nodules are met with in other diseases. Besides the 
tubercle there are inflammatory lesions occurring between the tubercles 
and varying with the anatomical character of the organs affected. Thus 
in the lungs the tubercle may be inconspicuous, whereas the pneumonic 
infiltration of the lung tissue surrounding the tubercles and filling in 
the spaces between them gives the organ its most striking anatomical 
characters. There are instances of tuberculosis in which the whole 
process runs its course without the development of any definite tuber- 
cles. For example, in the lungs the inhalation of tubercle bacilli in con- 
siderable numbers may be followed by rapid tuberculous pneumonia 
without definite tubercles, and in other situations similar results may be 
produced. In the further progress of a case of tuberculosis caseous 
change is important. This may present itself in the form of areas of 
considerable size having a dull, opaque, lusterless, grayish or whitish 
character, and not inaptly likened to the appearance of cheese. These 
centers of caseous necrosis may finally become liquefied, and cavity 
formations may result. These changes are particularly frequent in 
tuberculosis of the lungs, less frequent in bones, skin, glands, or kidneys. 
In connection with tuberculosis of bones there may be formed small 
or large cavities filled with liquefied caseous or puriform material. 
These may involve the surrounding tissues as well as the bones them- 
selves. The term "cold abscess" is* applied to them. Small tuberculous 
areas and sometimes even large foci are prone to be surrounded by 
reactive fibrous-tissue hyperplasia, and thus a complete encapsulation 
may result. Small foci may be uniformly transformed by organization of 
proliferating connective tissue and may be thus entirely healed. In 
other cases simple encapsulation occurs, the tuberculous mass within 
perhaps undergoing calcification. These changes will be more particu- 
larly referred to below. 

Tuberculous lesions of the mucous membranes frequently begin 
with the formation of distinct tubercles occupying the deeper layers 
of the mucosa or the submucosa. These by confluence may form con- 
siderable areas of tuberculous disease, while at the same time reactive 
inflammation of the surrounding tissues adds to the mass. Sooner or 
later ulcerative changes upon the surface make their appearance, and 
irregular, more or less necrotic, ulcers result. The caseous appearance 
of these and the occurrence of distinct tubercles in the edges or base 
manifest the character of the process. 

The histogenesis and anatomy of the tubercle has been considered 
on page 141, and we shall only here consider its pathological relations. 

After the establishment of the local lesion of tuberculosis in any 



320 



A TEXT-BOOK OF PATHOLOGY 



part of the body two opposing tendencies struggle for supremacy: the 
tendency of the tuberculous disease to spread and the tendency of the 
normal tissues to encapsulate or limit the spread of the invading disease. 
In most cases the former succeeds and the secondary tubercles first 
appear in adjacent parts, the transportation of the bacilli from the 
primary to the secondary focus being accomplished either by the flow 
of the lymph or juices of the body, by continuity, or by the activity 
of phagocytes. The last take from the edges of the tubercle some 
of the bacilli and transport them either by their own ameboid activ- 
ities or in the lymph-stream to neighboring parts, where they them- 
selves fall victims to the organisms they have appropriated, and thus 
deposit the germs of new foci of disease. The dissemination of tuber- 
cles to more distant parts may occur in various ways. In the case of 
tuberculosis of the mucous membranes bacilli may be cast off from the 
surface and spread to other parts of the mucous tracts with the contents 
of these, as in the case of tuberculosis of the gastro-intestinal tract. In 
the case of pulmonary lesions the ulcerative processes, or attacks of 
coughing, may loosen infected particles from lesions of the bronchi, 
and the deep inspiratory efforts following the cough, or the ordinary 
inspirations, may carry the bacilli into the finer bronchioles, where new 
foci arise. If the tuberculous lesions involve the walls of the lymphatics, 
particularly the larger lymph-channels, like the cervical or thoracic 
ducts, bacilli may gain access to the lymph-stream and thus be trans- 
ported to the venous circulation, and then through the heart to the lungs 
or perhaps to other organs. When the tuberculous lesion invades the 
wall of a vein the dissemination of the bacilli is even more rapid and 
widespread, as the organisms find their way to the heart by a more 
direct route. In rare instances an artery is invaded and the organisms 
are scattered through the terminal distribution of this. The lesions 
of vessel walls arise either as primary tubercles, as extension processes, 
or secondary to intimal lesions leading to thrombosis, a condition which 
favors the settling of tubercle bacilli. Upon surfaces the disease may 
spread by direct continuity or by the movements of the body. Thus, 
lesions of the peritoneum may become almost universal in consequence 
of the peristaltic movements, though more frequently the extension 
occurs along the lymphatic channels. 

The condition which results from general infection and formation 
of tubercles in various situations is known as miliary tuberculosis. 
In these cases the progress is usually rapid and a fatal termination is 
not long delayed. The tubercles, therefore, remain small, and at autopsy 
are still typically gray miliary tubercles. Sometimes, however, miliary 
tuberculosis may assume a more chronic form, perhaps in consequence 
of the gradual admission of bacilli to the circulation and the formation 
of small crops of tubercles during a considerable period of time. 

Occasionally, tubercle bacilli invade the blood and do not give rise 
to miliary tuberculosis. Why they do not is not clear. 

Miliary tuberculosis may be local or general. In the former case 
the bacilli are admitted to the vascular distribution of a restricted 



DISEASES DUE TO BACTERIA 



321 



area only; in the latter, widespread dissemination through the blood 
occurs, and practically all parts of the body may be involved. Local- 
ized miliary tuberculosis is most frequent in the lungs. 

The progression of tuberculosis is accomplished by the coalescing 
of formed tubercles or an exaggeration of the inflammatory characters, 
especially in the presence of mixed infection, or to both. Regressive 
tuberculosis "is either latent (q. v.) or cicatrizing. The latter is that 
form in which the most pronounced lesion is fibrous tissue formation, 
which may or may not finally wholly replace the tuberculous tissue. 
Such a process is responsible for the healing of tuberculosis. It has 
been asserted that two-thirds of all adults have some such healed lesion 
of tuberculosis in them. 

The healing of tuberculous lesions follows the general rules of repair. 
The fibroblasts grow both within and without the tubercle and gradu- 
ally replace it. Wherever fibrin has been deposited the tubercle grows 
and attempts to form a new tubercle. It is noteworthy that in healing 
of tuberculosis a great amount of fibrous tissue is produced and ad- 
hesions are common. 

Seats of Tuberculosis. — Among the frequent situations in which 
tuberculosis makes its appearance are the lungs, the lymphatic glands, 
the bones and joints, the mucous membranes, particularly those of the 
larynx and intestines, the serous membranes, the prostate, testicles, 
ovaries, Fallopian tubes, kidneys, uterus, suprarenal capsules, brain, 
liver, spleen. In some of these situations the lesions are practically 
always secondary, as, for example, in the liver and spleen. In others 
they are most frequently primary, as in the lungs. The occurrence of 
primary tuberculosis in the internal organs may be difficult to explain. 
It is possible, however, for the bacilli to gain access to the lymphatic or 
blood circulation without causing a lesion at the point of entrance. Their 
deposit in some internal organ then occasions the first or primary focus 
of disease. Thus, primary tuberculosis of the mesenteric glands, of the 
lymphatic glands of the neck, or of the postbronchial glands may occur 
without primary disease of the intestines, of the mouth or skin, or of the 
lungs in the several instances. Similarly, primary tuberculosis of the 
kidney or of the suprarenal capsule may occur without any evidence of 
the point of entrance of the micro-organisms. In some cases, of course, 
the primary lesion may be so small and in such a hidden situation that it 
escapes notice. 

After the discovery of the tubercle bacillus a number of diseases 
not previously recognized as tuberculous became identified as forms of 
this disease. Among these is lupus vulgaris of the skin. The histological 
examination shows numerous tuberculous granulations, sometimes ar- 
ranged in striate fashion along the small blood-vessels of the skin and 
containing epithelioid and lymphoid cells and giant cells. The presence 
of the bacilli and the proved infectiousness of the tissue, with the 
histology, render the nature of this disease certain. The warty forma- 
tions frequently acquired by anatomists at points of injury have like- 
wise been shown to be in many cases due to tuberculous infection. 
21 



322 



A TEXT-BOOK OF PATHOLOGY 



Scrofula, which was formerly regarded as a special condition prediposing 
strongly to tuberculosis, is now regarded as actual tuberculosis. The 
scrofulous glands of the neck constitute tuberculous adenitis, the infec- 
tion in many cases gaining access through the mucous membranes of 
the mouth and pharynx or through the skin. Scrofulous rhinitis and 
sinuses have similarly been shown to be forms of tuberculous disease. 
Many cases of joint disease regarded as scrofulous are likewise dependent 
upon the action of the tubercle bacillus. 

Latent Tuberculosis. — A tuberculous lesion may become encap- 
sulated and limited in its extent before it has invaded tissues widely, 
and may so remain for years without giving rise to manifest clinical 
symptoms. Subsequently, however, the encapsulating membrane may 
be penetrated and widespread infection, local or general, may occur. 
Such latent tuberculosis is particularly frequent in the postbronchial 
glands. These glands are often found enlarged at autopsies in which no 
tuberculous disease of other organs is found. Injections of emulsions of 
such glands in a notable proportion of cases produce tuberculosis in 
guinea-pigs, and thus it has been determined that the glands in question 
are frequently the seat of latent tuberculous disease. The existence of 
such lesions explains the cases of sudden generalized miliary tuberculosis, 
in which no primary focus of the disease was recognized during life. 
It is perhaps well to emphasize the difference between latent and healed 
tuberculous foci. The former are arrested and surrounded by a limiting 
wall of connective tissue through which it is possible for degenerations 
or inflammations to extend and free the tubercle bacillus, or awaken it 
to activity, while in healed foci it is assumed that all infective agents 
have been destroyed, and the original lesion wholly replaced by fibrous 
tissue. 

Pathological Physiology. — The effect of tuberculosis upon the gen- 
eral health varies greatly. Undoubtedly the bacillus contains or is capable 
of producing toxic substances that have an effect upon the general organ- 
ism; the nature of these, however, still remains undetermined. The 
tuberculin of Koch, a glycerin extract from cultures of the tubercle bacil- 
lus, produces fever with the general symptoms characteristic of pyrexia 
and local reactive changes in existing tuberculous lesions. Among the 
latter, redness or increased vascularization of the tubercles, and soften- 
ing or necrosis of the cells surrounding the bacilli, are most important. 
The last named change deters the growth and multiplication of the 
bacilli themselves, but at the same time makes their escape from the 
focus of disease more easy and thus exposes the individual to the liability 
of general infection. The active substance contained in tuberculin is 
probably a thermostabile polypeptid that is destroyed by pepsin and 
trypsin, but not by erepsin. It is positively chemotactic for leukocytes. 
It does not act upon the tubercle bacillus directly and is not an anti- 
toxin. The tubercle bacillus seems able also to excrete lipase during 
its vegetative life. In addition to this, the tubercle bacillus in its dead 
state contains some body or bodies capable of influencing the organism, 
as was shown by the experiments of Prudden and Hodenpyl, who 



DISEASES DUE TO BACTERIA 



323 



were able to produce nodular lesions by injecting dead bacilli into the 
circulation of animals. Mention has already been made under Caseation 
of the unsaturated fatty acids of tubercle bacilli in the production of 
necrosis. Such substances are also present in dead bacillary bodies. 
These lesions, of course, are not strictly tuberculous, though they 
possess some elements of the natural tubercle. It is altogether prob- 
able, however, that in addition to the tuberculin of Koch and the 
chemotactic substances contained in the body of the tubercle bacilli, 
there are other poisonous substances produced by the growth and 
multiplication of the bacilli in the tissues, that lead to a general de- 
terioration in the health of victims of this disease. Trudeau, Pear- 
son and Gilliland, and others have been able to immunize animals 
by repeated inoculations with bacilli of lowered virulence. Human 
bacilli if injected into cows will raise their resistance to virulent bovine 
bacilli. A form of immunity called "isopathic" (Behring) is thus pro- 
duced. The sera of such immunized animals is not protective or cura- 
tive to other animals. 

None of the supposed "antitoxic" sera thus far produced has been 
proved to have antitoxic or immunizing power. 

Tuberculosis is primarily a local process, but influences the general 
organism by its direct effect upon the organic functions of the parts in 
which it is located by the development of these as yet unknown toxic 
substances, and later by the widespread infection of the organism. 
Amyloid disease is a sequel of prolonged tuberculosis. The mechanism 
of defence against tuberculosis is only partly known. In the case of 
local lesions of the lungs or other parts the reaction of the tissues prob- 
ably resulting from the activity of chemotactic substances in the body 
of the bacilli themselves, or of similar substances produced by the 
cellular necrosis, leads to the formation of an embankment of cellular 
or fibrous tissue that serves to hold the disease in check. Subsequently, 
the disease may be wholly eradicated by degenerative changes terminat- 
ing in calcification. That such favorable results are not uncommon is 
proved by the frequent occurrence at autopsies of small sclerotic or 
calcareous areas in the lungs. Tuberculosis is frequently cured in these 
early stages, but after it has reached the degree of intensity or the wide- 
spread character that makes it recognizable by our present methods of 
physical examination, the reactive processes are usually no longer able 
to cope with its progress. 

The defensive reactions of the blood against the tubercle bacillus 
are not very potent. In the serum there appear agglutinins, opsonins, 
and a complement-fixing body in excess of those found in non-infected 
persons. Use is made of the opsonins in bacterin therapy, as it is possi- 
ble to increase their strength by injection of some of the products of the 
tubercle bacillus or of killed cultures. Repeated injections of the bacilli 
or their products into lower animals have not developed any valuable 
antiserums for therapeutic purposes, but claims have been made that 
active immunization with living bacilli will raise the resistance of 
animals and man. Such methods are, to say the least, hazardous. 



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PSEUDOTUBERCULOSIS 

This name has been applied to conditions occasionally met with 
in which nodular lesions resembling tubercles, but containing micro- 
organisms of different kinds, have been found in the liver, kidneys, and 
other organs. Pseudotuberculosis is not a specific disease, as a number 
of distinct infections assume this pathological character. Among the 
organisms isolated are various streptothrices and acid-proof bacilli 
resembling the tubercle bacillus to some extent (see below). In the 
lower animals, and very rarely in man, certain animal parasites cause 
lesions of the same kind. 

The Smegma Bacillus. — A bacillus quite closely resembling the tubercle bacillus 
was discovered in the smegma and later on the skin of various parts of the body. 
It not only resembles the tubercle bacillus morphologically, but behaves in a similar 
manner toward stains. In particular this bacillus holds its stain when attempts are 
made to decolorize with acids. The bacillus is frequently found in urine, and thus 
may cause an erroneous diagnosis of tuberculosis of the kidney or bladder. It 
may usually, though not certainly, be distinguished by its easy discolorization with 
absolute alcohol. 

Other Acid-proof Bacilli. — Several other bacilli that are refractory to decoloriza- 
tion with acid or alcohol have been discovered in milk and butter, in sputa, and in 
purulent or gangrenous collections in the lungs and elsewhere. Injections of pure 
cultures of some of these cause fibrinous inflammations in the peritoneum of guinea- 
pigs and rabbits, or pseudotuberculous formations, but not the specific lesions of 
tuberculosis. 

The lesions resulting from inoculation with acid-fast bacilli show a striking 
resemblance to those of tuberculosis, and only a careful microscopical examination 
serves to distinguish them. Examined with a microscope, the lesions of this spurious 
tuberculosis present a more inflammatory appearance and show a tendency toward 
abscess formation. In very rare instances, however, an approach toward the typical 
histologic conditions of genuine tuberculosis, characterized by the formation of 
giant cells, epithelioid cells, and caseation, is seen in this form of pseudotuberculosis. 

The causative organisms in such infections range in a biological series from short, 
bacillary, rigidly acid-fast forms very like tubercle bacilli to longer threads slightly 
acid fast, to groups of higher bacteria growing in mycelia and not acid fast, related 
to actinomyces and streptothrix. 

The streptothrices may produce infiltrative and proliferative lesions like the 
organisms just discussed. They have been found in various parts of the body as 
the causative factors in abscesses. The lung process is infiltrative, then suppura- 
tive, then necrotizing. Some of the streptothrix infections may resemble pul- 
monary tuberculosis and can be diagnosed only by isolating the organisms or by skin 
tests. It has been found possible to differentiate the various infections with these 
higher bacteria by means of skin tests. Preparations made from cultures of the 
various organisms, tubercle bacilli, partly acid-fast organisms, and those of strepto- 
thrix type, are rubbed upon an abraded skin surface; a swollen red area will arise in 
response to the preparation made from the causative bacterium and not to others. 

Pneumonomycosis aspergillina. — In man and in animals pulmonary infection with 
forms of aspergillus, especially Aspergillus fumigatus, may occur in a pseudotubercu- 
lous form. The lesions are exudative and proliferative, and central caseation may be 
conspicuous. The fungi which belong to the group of hypkomycetes are readily dis- 
tinguished by the abundant mycelial threads and the conidia. Infection of other 
organs may occur spontaneously or experimentally. 

Pharyngomycosis leptothricia. — The Leptothrix buccalis is a normal 
inhabitant of the mouth, and occasionally produces a pathological lesion 



DISEASES DUE TO BACTERIA 



325 



of clinical interest. The organism probably belongs to the group of 
pleomorphic bacteria, though its exact position is not determined. It 
consists of fine threads, of wavy or spiral character, composed of rod- 
like segments. Occasionally spore-like bodies are found at the free ends 
of the filaments. The organism sometimes penetrates and multiplies in 
the crypts of the pharynx, causing a chalk-like nodule or deposit. 
Secondary inflammation may be occasioned. (See also Diseases of 
the Pharynx.) 

FOWL-TUBERCULOSIS 

Tuberculosis in various forms of fowl and birds (avian tuberculosis, 
Tuberculosis gallinarum) is a disease similar to, but not identical with, 
human tuberculosis. The spontaneous disease of birds occurs most 
frequently in the liver, the lungs being never primarily involved. In 
the liver are found nodules composed of a large central necrotic area 
sprinkled with chromatin debris surrounded by a zone of large epithelioid 
cells containing numerous nuclei, intermixed with small round cells. 
Tubercle bacilli are present in enormous numbers. The structural and 
cultural differences of the human and avian bacilli have been discussed 
on page 315. 

Despite the similarity of the bacilli of the human and avian types 
of tubercle bacilli, it does not seem that the latter can produce tubercu- 
losis in man. In the few cases in which avian bacilli have been isolated 
from human lesions, the simultaneous presence of human bacilli was 
not satisfactorily excluded. 

Experimental inoculations of bacilli isolated from the spontaneous 
disease will produce the same disease in birds; but if animals, such as 
guinea-pigs or dogs, which are very susceptible to human tuberculosis, 
are inoculated, they frequently resist infection, though they occasionally 
succumb to very large doses. In the latter case tubercles are usually 
absent, but large numbers of bacilli are found in the organs and in the ab- 
scesses which result at the point of inoculation. According to Nocard, rab- 
bits show a marked degree of susceptibility to this form of tuberculosis. 

Although there is no doubt that fowl in some instances have become 
infected through human sources, yet experimentally they exhibit a 
very high degree of resistance to human bacilli. If, however, the human 
bacilli are passed through birds for three or four generations, or are 
placed in the peritoneum of fowl in collodion sacs, for the same length of 
time, the virulence to birds is not only heightened, but the bacillus 
changes in its structural and cultural characteristics, assuming those 
of the bacillus isolated from spontaneous avian tuberculosis. The 
same is true of avian bacilli when these are inoculated in animals sus- 
ceptible to human bacilli. With each passage through such an animal 
the virulence of the bacillus is increased, and the form and cultural char- 
acteristics become more and more like those of the human bacillus. 
From these experiments it appears that the avian tubercle bacillus 
is only a modification of the ordinary tubercle bacillus caused by its 
growth in the tissues of the bird. 



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LEPROSY 

Definition. — Leprosy, lepra, or elephantiasis Graecorum, is an 
infectious and mildly contagious disease caused by a specific bacillus, 
the Mycobacterium leprae, discovered by Hansen. 

Etiology. — The essential cause of leprosy is a bacillus which closely 
resembles the tubercle bacillus, though it is less frequently curved and 
is somewhat more easily stained. Further, it differs in its grouping 
in the tissues and in its character of growth. The organism is usually 
found in large numbers in the leprous lesions and in the nasal mucus, 
whether there be definite leprous ulcerations in the nose or not. In the 
tissues the bacilli are found within large cells of the specific granulation 
tissue (lepra cells). In the anesthetic form it is found in the nerves 
and central nervous tissues. The organism has been demonstrated in 
the blood in certain cases of the tubercular type. It is readily stained 
by any of the methods applicable for the tubercle bacilli or by Gram's 
method. It frequently shows light areas like those of the tubercle 
bacillus; these have been regarded as spores, but are more probably 
produced by fragmentations, as in the case of the tubercle bacillus. 

Musgrove, Clegg, and Duval have succeeded in cultivating the 
leprosy bacillus upon media containing tryptophan. The organisms 
do not possess the power of digesting the protein molecule to liberate 
this substance, so that it must be introduced artificially or supplied 
to them by means of symbiotically growing amebse or bacteria. Two 
kinds of cultures have been observed, one growing in a luxuriant yellow 
form, the other as a scanty, almost colorless colony. The importance 
of the two is not yet understood. Some believe that the scanty growth 
is the true lepra bacillus. Wolbach and Honeij's work upon human and 
rat leprosy would suggest that four kinds of organisms — diphtheroids, 
pigmented acid-fasts, non-pigmented acid-fasts, and anaerobics — have 
been cultivated in different parts of the world. It would seem that 
they may all be involved, or that two are present as varying examples 
of one organism. What has been called typical leprosy has been pro- 
duced in rabbits' eyes, mice, and especially monkeys. Flies of the genera 
Musca and Stomoxys have been accused of carrying lepra bacilli. In 
one case the disease has been given to a condemned criminal by direct 
inoculation. 

Besides the specific bacillus, other conditions are important in the 
etiology. Thus, the disease flourishes in certain localities extensively 
and little in other places. It is uncommon in the United States, but some 
of the Gulf States, particularly Louisiana, have considerable colonies, 
and in the Northwest and on the Pacific Coast it is met with among the 
Norwegian and Chinese immigrants. In Mexico, South America, Nor- 
way and Sweden, India, and other Asiatic countries it is common, and 
the Sandwich Islands are particularly affected. During the Middle 
Ages it flourished in Europe as a universal scourge, unsanitary conditions 
probably acting as the predisposing cause. Certain articles of diet are 
believed to occasion it, particularly fish; this view, however, lacks proof. 



DISEASES DUE TO BACTERIA 



327 



The disease must be regarded as contagious, though less so than 
tuberculosis. Intimate association for a long time seems to be necessary 
for its transference. Insects have been thought to transmit the disease, 
but proof is as yet not forthcoming. It is probably transmitted from 
parent to offspring in rare instances. The bacilli have been found in 
the hyalin substance, the syncytial cells, chorionic villi, and vessel 
walls of the placenta. 

The importance of the nose as a seat from which leprosy bacilli 
are disseminated is emphasized by the facts that the bacilli are present 




Fig. 115. — Nodular leprosy (Goldschmidt). 



here even when no leprous lesions exist, and that ulcers are common on 
the septum. The lesions when present are softer than those on the 
skin and may be found in both the tubercular and anesthetic forms. 

Pathological Anatomy. — Leprosy presents itself in two forms — 
the tubercular and the anesthetic. In the former there are developed 
in the skin of the face, the extensor surfaces of the elbows and knees, 
about the hands, or less frequently elsewhere, small or large nodular 
elevations. These at first are reddish in color, with apparent inflam- 
matory reaction. Later they lose their redness and remain as indolent 
lesions that grow very slowly or remain stationary. They may break 



328 



A TEXT-BOOK OF PATHOLOGY 



down, forming ulcerations which do not readily heal, or they may be 
gradually converted into fibrous cicatricial tissue, causing unsightly 
deformities of the skin. The appearance of the patient's face is highly 
characteristic, and is known as leontiasis leprosa (Fig. 115). The mucous 
membranes and some of the internal organs may be involved. The 
anesthetic form is usually marked by less conspicuous lesions, but sub- 
jective symptoms, such as hyperesthesia and neuralgic pains, and 
later ulcerations partly trophic in nature, may make it a more serious 
variety. In the skin there are found whitish or brownish spots, slightly 
if at all elevated or altered in consistency. Later, ulcerations may 
appear. Very commonly the anesthetic and tubercular varieties are 
coexistent. 

The chief seats of the leprous nodule are in the corium and sub- 
mucous tissues. It invades, by cellular extension, the adjacent nerves, 
vessels, muscles, and sweat-glands, and may be found in the epithelial 
coverings. 

The nodules occurring in the liver, spleen, and testes in this disease 
are admitted to be similar to the nodules of the skin ; those found in the 
lungs, kidneys, and intestines, as well as those of the serous surfaces, 
are believed by many to be tuberculous and the result of secondary 
infection. These two diseases are certainly frequently associated; 
probably 40 per cent, of the cases of lepra become tuberculous. 

Other forms of secondary infection occur. Thus injuries of super- 
ficial lesions may allow pyogenic infection, and extensive ulcerations 
and gangrenous necrosis may ensue. The terms lepra mutilans and 
lepra gangrenosa are applied to such; and various micrococci and sapro- 
phytic organisms have been discovered in such cases. The histology 
of leprosy is given on p. 147. 

Pathological Physiology. — Infection with the lepra bacillus leads 
to local rather than general disturbances. The toxins of the disease, if 
such there be, are not of great virulence, and constitutional symptoms 
are, therefore, wanting as a rule. In the later stages fever and other 
systemic disorders may be occasioned by secondary infections. A 
supposed antitoxic substance has been prepared and has been largely 
used. It is impossible to claim or disclaim the antitoxic nature of this, 
as no toxins have as yet been isolated or obtained in any form, and 
the supposed antitoxic substances cannot, therefore, be tested. 

In the anesthetic form it was formerly customary to regard the 
pigmented or light-colored spots as a result of trophic disturbance, and 
more destructive lesions, such as ulceration and gangrene, received a 
similar explanation. Recent investigations, however, seem to show 
that in these cases there is usually from the first a leprous change in 
the tissues due probably to thickening of vessel walls, and that sec- 
ondary infections frequently play a part, though trophic disturbances 
must still be admitted to a certain extent. 



DISEASES DUE TO BACTERIA 



329 



BACTERIUM MUCOSUM CAPSULATUM GROUP 

This is a very large group, chiefly saprophytic, in the intestinal 
tract of men and animals, but includes a few important highly patho- 
genic varieties. They are all Gram-negative, non-motile, blunt-end 
rods, growing luxuriantly on artificial media, and with active ferments 
against carbohydrates. Some possess capsules in the body only, 
others in certain artificial media as well. Perkins divides them into 
three convenient groups: 

(a) The Bacterium aerogenes type ferments all carbohydrates, with 
the formation of gas. 

(6) Bacterium pneumoniae type ferments all except lactose, with gas. 

(e) Bacterium lactis aerogenes ferments all as above, except saccha- 
rose. 

This order represents their frequency and pathogenicity. The 
first class is found in abscess, pneumonias, and inflammations of serous 
membranes. The most important member of the second group is 
commonly called "Friedlander's bacillus," an organism seldom found 
aside from pneumonia. (See Friedlander's Pneumonia, p. 283.) The 
third group contains very few pathogenic varieties, but is most com- 
monly concerned in milk souring. 

The exudates caused by all the pathogenic members of this group 
have one or both of two characters. The exudate may be viscid or 
it may contain swelled up cells in which the organisms lie (Mikulicz 
cells and swollen cells of Friedlander's pneumonia). The bacteria pos- 
sess a mild lytic effect upon epithelium and endothelium. The organ- 
isms give rise to very few antibodies. 

A very important non-pathogenic organism not far removed from 
the third division is the Bacterium bulgaricum of Massol. This breaks 
up the carbohydrates of milk and produces lactic acid. This is recom- 
mended by Metschnikoff as an intestinal antibacterial agent. 

Other Organisms of Less Importance 

The Bacillus pyocyaneus is a Gram-negative, occasionally pathogenic organism 
found in pus having a bluish or greenish color. The bacillus is small in size, fre- 
quently occurring in chain formation, and is actively motile. 

Upon artificial media it produces colored growths and a soluble pigment, which 
gives to the culture-medium for some distance from the growth a greenish, or in 
some cases a dark blue, coloration. The organism in pure culture is highly virulent, 
producing intense suppurative inflammations. Occasional instances of general pyo- 
cyaneus infection have been observed. In these cases there are most commonly 
thin purulent exudates in serous cavities and cellulitis. 

The organism acts destructively upon other bacteria, so that a fatal dose of 
Bacillus anthracis may be rendered innocuous by the simultaneous injection of 
B. pyocyaneus. The destructive effect has been demonstrated in vitro. It seems 
dependent on ferments as well as intracellular substances contained in the bacillus. 
The toxin is hemolytic and parenchymatous degeneration arises in the liver, kidneys, 
etc. 



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Diseases Due to Spirilla 

CHOLERA 

Definition. — Cholera is an acute infectious disease caused by a 
spirillum or vibrio. 

Etiology. — The specific cause of cholera is the Spirillum or Vibrio 
cholerce asiaticce. This organism is frequently spoken of as the comma 
bacillus of Koch. It is a short rod, from 0.8 to 2 [i in length, and usually 
somewhat curved. The term "comma bacillus" is applied to it on 
account of the latter fact. It is found abundantly in the rice-water 
discharges of choleraic patients, and is not rarely arranged in threads, 
though the vibriones are not actually attached to one another (Fig. 116). 
It is motile, the motility being due to a single flagellum attached at one 
end. In artificial cultures the organisms are actually joined to form 




Fig. 116. — Spirillum of Asiatic cholera, from a bouillon-culture three weeks old, showing 
numbers of long spirals; X 1000 (Frankel and Pfeiffer). 

spirals of greater or less length, and these may present a rapid rotary 
movement. 

The demonstration of the cholera spirillum is usually easy, as ordi- 
nary stains color it intensely. It is Gram-negative. Even the flagel- 
lum may be stained by the ordinary stains, though more definitely 
shown by special methods. 

The cultivation of the spirillum is usually easy. Cultures may be 
obtained upon agar-agar, blood-serum, or other media, but the gelatin- 
culture is most characteristic. In puncture-cultures the growth occurs 
along the entire length of the puncture, but particularly at the top, 
where the supply of oxygen is abundant; and the gelatin becomes lique- 
fied. This gives rise to a peculiar nail-shaped or funnel-shaped forma- 
tion (Fig. 117). In plate-cultures the growths first appear in the lower 



DISEASES DUE TO BACTERIA 



331 



strata of the gelatin as small granular whitish spots which extend toward 
the surface, liquefy the gelatin, and thus produce excavations. The 
appearance to the naked eye suggests small air-bubbles in the media. 
Under low powers of the microscope the culture is seen to be coarsely 
granular, the size of the granules varying with the age of the culture. 
The bottom of the growth presents an appearance like that of a surface 
sprinkled with poAvdered glass. 

When grown in bouillon or other liquid media the cholera microbe 
produces nitrites and indol so abundantly that the addition of a little 
pure sulphuric acid or hydrochloric acid (without nitrite solution) leads 
to a reddish coloration — "cholera-red." The indol 
reaction is not absolutely diagnostic, since other 
spirilla may cause it. Negatively, however, the test 
is extremely useful, since its absence excludes the 
cholera germ. A definite quantity of peptone is 
necessary to make the test reliable. Therefore, in- 
stead of bouillon an alkaline 1 per cent, peptone 
solution containing 0.5 per cent, of sodium chlorid is 
preferable (Dunham). 

The cultures of cholera grow best at a temperature 
about that of the body, but they may thrive at much 
lower degrees of heat. Exposure to a temperature of 
52° C. (125.6 °F.) for four minutes may cause their 
destruction, but ten or fifteen minutes' exposure at 
55° C. (131° F.) does not always prove destructive. 
They may thrive in distilled water or in water con- 
taining saline matter; in or upon various forms of 
food; upon clothing, and the like. The resistance, tur^-cuiture in U gei- 
however, is not very great, and this has been urged Solera ^sSP- hours 
as an objection to the likelihood of the organism being ld (Shakespeare), 
the cause of a disease having such evident tenacity. 

Distribution. — The cholera spirillum is found in the intestinal con- 
tents and mucosa. The organism is not found in the blood nor in any 
organ or tissue except the gastro-intestinal tract. 

The pathogenicity of the cholera spirillum is now admitted uni- 
versally. Injected into the peritoneum of animals it causes a rapid 
fall of temperature, abdominal tenderness, and collapse. The perito- 
neum shows signs of beginning inflammation, and the organisms are 
found in abundance within the cavity. It has been possible also to pro- 
duce intestinal changes almost if not identical with those of human 
cholera in animals by arresting the peristalsis of the intestines with 
injections of opium, rendering the liquids of the stomach alkaline 
with sodium carbonate, and then' feeding cultures. In man a few 
auto-infections have occurred, the experimenter swallowing cholera 
cultures. In one case at least typical cholera was admitted by Petten- 
kofer, the most important opponent of the acceptance of this germ, as 
the specific cause. The celebrated case of Dr. Oergel, who died as a 
result of laboratory auto-inoculation, seems practically conclusive. 





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A TEXT-BOOK OF PATHOLOGY 



Other Causes Operating in Cholera. — Infected water is the chief 
source of transmission of cholera. The microbe may live in water for 
months. It is said that the Ganges River contains the spirilla constantly. 
Certain climatic conditions favor the development of the disease. Thus it 
is constant in certain regions of India, and spreads thence when the con- 
ditions become favorable. The evidence shows that the germ is carried 
by individuals, or by infected food and the like. The disease flourishes 
in warm seasons of the year, and an epidemic is usually brought to a 
close by winter frosts. 

Individual disposition plays a part in the occurrence of the dis- 
ease, for the germ is easily destroyed by the acid gastric secretions, 
and infection is, therefore, most likely to occur when gastro-intestinal 
derangements furnish a favorable predisposition. 

Pathological Anatomy. — The lesions of this disease are found 
in the intestinal tract, and will be described in the appropriate 
section. 

Secondary lesions of other organs are met with in severe cases, 
and result from the circulation of toxic substances produced by the 
bacillus. 

Pathological Physiology. — A number of toxins have been isolated 
from the blood of cholera patients and from cultures. The exact nature 
of these and the relations of the several forms remain to be determined. 
It is certain, however, that toxins produced in the intestinal tract give 
rise to many of the symptoms of the disease. Injection of the filtrate 
of cultures causes collapse and other symptoms like those of the algid 
stage of the disease. The principal toxic substance seems to be closely 
attached to the organism itself (endotoxin), but a secreted extracellular 
toxin may also be found in the culture fluid when the organisms are 
enclosed in a collodion sac. The human or animal organism in some 
way develops immunizing or protective substances in the course of 
infection, and it has been found possible by a process of vaccination 
with cultures of gradually increasing virulence to protect animals and 
human beings from the disease. Haffkine's protective vaccination 
of human beings yielded very encouraging results. He at first used 
an attenuated culture and then one of high virulence. The injections 
are made under the skin, where the spirilla soon die, but their bodies 
set up the antibodies. He inoculated 200,000 persons in India. Pfeiffer 
found that the serum of animals so vaccinated had a distinct action 
upon cholera spirilla, causing their agglutination or destruction, and 
possibly in this way exercising a protective influence. These antibodies 
may be used to diagnose a case of cholera, either by agglutination, 
like the typhoid Widal test, or by the Pfeiffer intraperitoneal test. 

The rapid and copious intestinal discharges of cholera lead to con- 
siderable inspissation of the blood, and doubtless contribute to the 
causation of some of the symptoms of the disease. Examination of 
the blood during the height of the malady may show greatly increased 
numbers of the red blood-corpuscles. 



DISEASES DUE TO BACTERIA 



333 



Organisms Resembling the Cholera Vibrio 

Spirillum of Finkler and Prior. — This organism was discovered by 
the investigators, whose names it bears, in the stools of a ease of cholera 
nostras. It resembles the vibrio of Asiatic cholera in its shape and 
somewhat in its manner of growth and its production of the indol reac- 
tion. It differs, however, in being somewhat longer and more slender 
and in coagulating milk when this is used as the culture-medium. 
The growth upon gelatin is more rapid, so that within twenty-four hours 
in the case of a puncture-culture the liquefaction has proceeded so far 
along the puncture that an elongated sac-like excavation is formed, in 
which turbid liquid is contained. It has not yet been proved that this 
organism has an etiological relation to cholera nostras ; its pathogenicity 
is improbable. 

Spirillum tyrogenicum is an organism discovered in old cheese by 
Denecke. It resembles the last-named variety very closely, and differs 
from the vibrio of cholera in liquefying gelatin quickly, though the 
rapidity is not so great as in the case of the Finkler and Prior organism. 

Spirillum Metschnikovii. — This organism was discovered by Gama- 
leia in the intestines of chickens affected with choleriform disease. It is 
somewhat shorter and thicker than the cholera spirillum. In culture it 
resembles the vibrio of cholera very closely, though the trained bacte- 
riologist can easily distinguish them. The organism is non-pathogenic 
for man, but chickens, pigeons, and guinea-pigs are highly susceptible. 

Besides these spirilla or vibriones which have been discovered in 
various diseases, a number of organisms that resemble closely the 
spirillum of cholera have been found in the water of streams supplying 
the drinking-water of cities. Among these Neisser described the Spiril- 
lum berolinense, obtained from the water of the Spree in 1893. Dunbar 
and Oergel isolated a similar organism from the water of the Elbe, 
and a number of others of like character are known. The relations, 
however, of the different forms to each other and the differentiation of 
these varieties have not as yet been definitely determined. 

Pathogenicity. — Some of the forms described produce violent 
gastro-intestinal disturbance and death in a certain proportion of ani- 
mals prepared by injection of opium and alkalinization of the intestinal 
tract with soda and then fed with pure cultures of the organisms. They 
are evidently highly irritating bacteria, and some remote relationship 
seems to exist between them. This, however, cannot be positively 
asserted. 

The separation of these forms from the true cholera spirillum is by 
no means easy. It is best done by the agglutination and bacteriolytic 
tests. For this purpose it is necessary to have the serum of an animal 
immunized against the cholera germ, and to this only the cholera spiril- 
lum will react. 



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A TEXT-BOOK OF PATHOLOGY 



Diseases Due to Spirochetes 
syphilis 

Definition. — Syphilis is a specific contagious disease of man, believed 
to be caused by the Spirochaeta pallida or Treponema pallidum. The 
disease does not occur spontaneously in any of the lower animals. 

Etiology. — Many organisms have been described for this disease, 
the most discussed being Lustgarten's bacillus and Schaudinn's spiro- 
chete. The former is a large rod, said to lie in and between the cells 
of lesions, of general tubercle-bacillus-like morphology. It has not been 
cultivated. It has now been given up as the cause of syphilis. 

In 1905 Schaudinn discovered an organism in syphilitic lesions 
which he named Spiroclmta pallida. Later during the same year and 
with the co-operation of Hoffman he was able to demonstrate the organ- 
ism in every case of uncomplicated syphilitic disease examined by him. 
The spirochete is described by Schaudinn (Fig. 118) as an extremely 




Fig. 118. — Spirochaeta pallida from chancre, stained by Levaditi's method; X 1500 
(Bulletin No. 1, Medical Department, U. S. Army, 1913). 

delicate, actively motile, faintly refractive, spiral, long, thread-like or- 
ganism, tapering at both extremities and terminating in pointed ends. 
It propels itself during life by rotating around its longitudinal axis, 
first in one direction and then in another. In the resting state undu- 
lating movements may be observed passing along the length of the 
organism, suggestive of an undulating membrane. In addition, bend- 
ing, twisting, twining, and whipping movements of the whole body may 
be noticed. The organism varies from 4 to 14 [i in length, ranging in 
thickness from a size too minute for measurement to 0.25 ^ in the largest 
specimens. The spirals range from six to fourteen in number; they are reg- 
ular, narrow and deep, corkscrew-like, and appear constantly so, no matter 
whether the specimen be derived from initial lesions, papules, lymphatic 
glands, spleen, etc., or from the scleroses of apes. The curves are large 



DISEASES DUE TO BACTERIA 



335 



arcs of a small circle, while other spirochetes occurring with the pallida 
show smaller arcs of a large circle. By means of Loffler's method 
of staining flagella a long delicate flagellum has been noted at each 
end of the organism; in some specimens two flagella at one end were 
seen, giving the appearance of an attempt at longitudinal division. 
Novy could find no evidence whatever of longitudinal division. Schau- 
dinn has failed to discover any signs of an undulating membrane or a 
nucleus in the stained specimens, though the latter has been reported by 
Wechselmann and Loewenthal in specimens examined with the aid of 
the ultramicroscope. At present there is some difficulty in distinguishing 
positively between the Spiroelwsta pallida and some common non-path- 
ogenic forms. Too much weight cannot, therefore, be given to the dis- 
covery of spiral organisms unless the investigator has had considerable 
experience. 

The Spirochata pallida has been found in the initial lesions, the 
secondary papules, the enlarged lymphatic glands, the mucous patches, 
the secretions, blood, and lately, by Noguchi, in the parasyphilitic dis- 
ease paresis. 

Many of the most conservative authorities accept this as the cause 
of syphilis. As will be seen below practically all of Koch's postulates 
have been fulfilled. 

Schaudinn maintained that the spirochetes are animal organ- 
isms belonging to the group of flagellates and proposed the name 
Treponema pallidum. The researches of Novy seem to be conclusive 
that this is not the case. He could find no evidence of an undulat- 
ing membrane, nucleus, or longitudinal division, and, on the contrary, 
only the transverse fission characteristic of bacteria. 

Wherever later studies place this spiral organism, certain characters 
have been made known by recent work suggesting its bacterial nature. 
It has now been cultivated by many persons after a technic elabor- 
ated by Noguchi. It grows anaerobically in colonies resembling those 
of bacteria and indicates its essential parasitic nature by requiring 
in this anaerobic culture fresh animal tissue. It does not require any 
intermediate stage to be infective, for, as we shall see, infection usually 
arises by direct contact, and, as the work of Noguchi has also shown, 
it will cause syphilitic lesions in rabbits' testes by inoculation of cultures, 
or of fresh material from human lesions. Syphilis can be produced in 
the anthropoid apes by inoculation of fresh human material or cul- 
tures upon the skin, and' a skin affection will result from the same 
treatment in the lower monkeys. When animals are infected with 
syphilis by experimental methods, the spirochete can be recultivated 
from their lesions. The cultures at hand develop a protein-like body 
which has some relation to the infection, because when a sterile solution 
thereof is applied to an abraded skin area an inflammatory papule 
results. This is the so-called "luetin reaction," and it has been used 
as a diagnostic test. The results of this and the Wassermann or 
complement-fixation test (q. v.) indicate the active antibody forma- 
tion on the part of the body. Agglutinins are also formed. All of 



336 



A TEXT-BOOK OF PATHOLOGY 



these recently discovered features favor a classification among the 
spirochetes. 

Whatever the nature of the organism, it is quite certain that the 
disease is definitely infective. In the great majority of cases infection 
occurs by direct inoculation in sexual intercourse. It may, however, 
be conveyed in many other ways. Physicians are sometimes infected 
in performing surgical operations or in examining syphilitic cases; 
persons have frequently been inoculated in the process of tattooing or 
vaccination when saliva or vaccine-lymph from diseased individuals was 
employed. Infection may be caused by kissing, or indirectly by the use 
of drinking-vessels which have been employed by the diseased. The 
newborn may be syphilitic in consequence of disease of the father or 
mother; and healthy wet-nurses may be infected by syphilitic nurslings. 
In addition to the specific cause, surrounding conditions and individual 
susceptibility doubtless play a part. During the Middle Ages this dis- 
ease at times and in certain places almost attained the character of a 
universal scourge. Its manifestations were severe, its course rapid, and 
in every sense its nature was malignant. Cases of this description are 
exceedingly rare at the present day. 

Pathological Anatomy. — The pathological course of this disease may 
be divided into three stages: the initial, the secondary, and the tertiary. 
The disease may abort at any stage, but such an occurrence is rare. 
Not infrequently, especially in women, the first and even the second 
stage as well may be overlooked. 

Chancre. — In the initial stage there is formed at the point of inocu- 
lation a primary lesion, commonly termed "chancre." This may make 
its appearance first as a somewhat red and inflamed papule, or as a 
vesicle which ruptures and thus produces an erosion. When it begins 
as a papule the surface soon becomes eroded, and thus a superficial 
ulceration is established. The peculiar feature of this lesion, to which 
Hunter called particular attention, is its hardness or induration, and it 
is by this feature largely that it is distinguished from the soft chancre 
or chancroid. The initial or primary lesion may remain indolent or as a 
small erosion for a long time, or it may soon cicatrize and leave a more 
or less definite scar. The chancre occurs upon the glans penis or prepuce, 
or within the urethra of the male; and in the vagina, urethra, or upon 
the cervix uteri and external genitalia of the female. Extragenital 
chancres may be observed in the rectum or anus, on the lips or tongue, 
tonsils or pharynx, the fingers, or other parts. 

Secondary Lesions. — At the end of a variable period of time after 
the eruption of the initial sore secondary manifestations of the disease 
make their appearance. The spread at first follows the lymph-channels, 
but when once the infiltrative lesions of the blood-vessels begin, as in late 
primary syphilis, the dissemination is by the blood-stream. The first 
secondary lesions, as a rule, are swelling and induration of the neighbor- 
ing lymphatic glands (syphilitic bubo). Later the superficial lymph- 
glands of the entire body become swollen and, like those in the neighbor- 
hood of the lesion, indurated. At the same time eruptions upon the skin 



DISEASES DUE TO BACTERIA 



337 



and mucous membranes make their appearance. The interval between 
the primary and the secondary manifestations is variable. Sometimes it 
is but a few weeks (three or four), at other times it may be several 
months. The manifestations of the secondary stage may begin with 
fever and constitutional symptoms, suggesting sudden and recent in- 
fection, and at the same time changes in the blood (rapid reduction of 
red corpuscles, moderate leukocytosis) make their appearance. Among 
the lesions of the skin various forms of papules, macules, and scaly 
eruptions are most frequent and characteristic. The lesions are usually 
symmetrically arranged on the two sides of the body and cause but little 
irritation. The color of the skin is frequently said to be somewhat 
coppery. On the mucous membranes and neighboring skin the most 
characteristic lesion of this stage is the condyloma latum, or mucous patch. 
This appears as a somewhat elevated patch with superficial erosion or 
ulceration. The surface has a necrotic appearance and may be cov- 
ered with more or less secretion. 




Fig. 119. — Gummata of the liver. 

Tertiary Lesions. — These may take the form of ordinary inflam- 
matory changes of the mucous membranes or of other parts, with a 
pronounced tendency to fibrous-tissue overgrowth and thickening, or 
of definite nodules — the syphilitic gummata, or syphilomata. Among 
the diffuse syphilitic changes of the tertiary stage may be ranked 
nodular thickening of the intima of the blood-vessels, certain changes 
in the liver, spleen, kidneys, and heart muscle, and also similar alter- 
ations in the nervous system. 

The localized lesions of the tertiary stage — the gummata — are 
most frequent in the bones (tibia, sternum, and skull) ; and in the in- 
ternal organs, such as the liver, lungs, kidneys, heart, and brain. 

The gumma presents itself as a nodular mass, varying in size from 
small tubercle-like formations (miliary gummata) to tumors the size 
of an orange or larger (Fig. 119). It is hard, and has frequently an 
elastic character, which has suggested the name "gummy tumor" or 

22 



338 



A TEXT-BOOK OF PATHOLOGY 



"gumma." On section, the substance is frequently found to be gelatin- 
ous or mucoid in appearance; but there is nearly always considerable 
induration, either peripheral, in the form of a capsular enclosure, or 
striate, in the form of bands extending from the center to the periphery 
and into the surrounding tissue. Occasionally gummata soften very 
rapidly and become converted more or less completely into puriform 
collections. When situated in the mucous membranes or adjacent to the 
surfaces of the body, suppurative, fatty, or necrotic softening may lead 
to the formation of superficial ulcerations. These may remain indolent 
or may gradually become cicatrized. Sometimes a gummatous lesion 
disappears entirely by absorption without leaving a trace of its ex- 
istence. 

The histology of syphilis is given on p. 145, among the specific 
infections, so that it is only necessary here to review the general features 
of the pathologic anatomy. The primary effect of the invasion of 
the spirochete is to injure the cells and incite round- and tissue-cell 
proliferation, followed by fluid and connective-tissue cell increase. 
The blood-vessels are attacked early and the spirochete characteristically 
excites endothelioid increase in all of the coats. The intimal changes are 
obstructive, leading to anemia and connective tissue replacement both 
in the vessel itself and the tissues supplied by it. The central necrosis 
of gumma is doubtless due to this. The fibrosis is largely due to the 
prolonged irritative effect of the spirals and to the debris of cellular 
destruction. Scars of considerable size are formed in the liver, brain, 
kidneys, etc., by the excessive scar tissue. The spirochetes seem to 
prefer those places where blood-supply and cellular activity are greatest, 
such as the bone-forming layer of the peritoneum and epiphysis and the 
sinusoids of the liver. Amyloid disease is frequently seen as the result 
of syphilis. 

Parasyphilis is a name given by Fournier to certain diseases, chiefly 
of the nervous system, in the clinical history of which syphilis is practi- 
cally always noted. The pathological lesions are similar but not identi- 
cal with those of syphilis, and some have doubted their luetic nature. 
Noguchi has lately found the Spiroch&ta pallida in the brain of paresis, 
a discovery which leaves hardly any doubt as to the syphilitic nature 
of this condition. He has, moreover, produced lesions in rabbits by in- 
jecting the brain of paretics. 

Pathological Physiology. — Syphilis is one of the most persistent 
of the infectious diseases, and occasions widespread changes that are 
doubtless toxic in character. The nature of the toxic principles, how- 
ever, is entirely unknown. In the tertiary stage pronounced anemia 
(cachexia) is frequent; and in the secondary stage rapid chloro-anemia 
with leukocytosis is quite common. 

Congenital Syphilis 

Syphilitic lesions may be found in the newborn or may develop 
some time after birth. Spirochata pallida and histological changes 



DISEASES DUE TO BACTERIA 



339 



of syphilis have been found in the placenta. Not rarely they occur in 
the newborn fetus and cause its premature death. Frequently there 
is maceration of the fetus prior to expulsion. The infection is in the 
ovum when the mother is infected before conception, and in the placenta 
when infection occurs during pregnancy. Among the lesions ob- 
served, sclerotic changes in the lungs, liver, spleen, pancreas, and other 
organs are conspicuous; and a certain condition of the bones is quite 
characteristic. The latter consists of a hyperplasia of connective tissue 
and fatty degeneration at the junction of the epiphyses of the long bones 
with the shafts. Various superficial lesions of the skin in the form of 
vesicles or bullae, fissures, and the like may be observed. The blood may 
present considerable excess in the number of leukocytes. An almost 
distinctive condition of second dentition is that known as Hutchinson's 
teeth. This consists of a notched indentation of the cutting surface of 
the upper central incisors. In addition, the teeth are often wedge 



shaped and peg-like (Fig. 120). All cases of inherited syphilis do not 
present this condition, and it occasionally occurs in non-syphilitic 
children. 



Definition. — Relapsing fever, or typhus recurrens, is an infectious 
disease caused by a specific organism which is found in the blood. 

There are four varieties, depending upon the biology of the spiro- 
chete concerned, but differing very little clinically: 

European relapsing fever, Spirochceta obermeieri; African relapsing 
fever, Spirochceta duttoni, transmitted by the tick Ornithodorus mou- 
bata; American relapsing fever, Spirochceta novyi; Bombay relapsing 
fever, Spirochceta carteri. 

The transmission of the first, third, and fourth is not known, but is 
probably due to some tick. Nicolle's result would indicate that the 
human form may be transmitted mechanically by the louse, but not by 
the biting of this parasite. Spirochceta obermeieri is described as the 
type. Opinion is still divided as to the proper classification. 

Etiology. — The Spirochceta obermeieri is a flexible spiral organism 
with six to twenty curves, in length several times the width of the red 
corpuscle (16 to 40 ^). It is found in the fresh blood, and presents active 
corkscrew, serpentine, and vibratory movements due to rotation and 
a flagellum-like extremity (Fig. 121). Recently it has been claimed 
by Schaudinn that this and other spirochetes belong to the group of 
flagellates (animal parasites) and are closely related to the trypanosomes. 
Novy's investigations appear to have completely disproved this view. 




Fig. 120. — Hutchinson's teeth. 



RELAPSING FEVER 



340 



A TEXT-BOOK OF PATHOLOGY 




The organism stains well with ordinary anilin dyes, but not by Gram's. 
The relation of this spirillum to the disease can hardly be questioned, 
as it is invariably present and appears in the blood during the paroxysms 

of fever and disappears in the intervals, thus 
showing its relation to the symptoms of the 
disease. In the case of Spirillum duttoni 
the female tick bites, becomes infective in a 
week, remains so all its life, and transmits 
the virus to the young. All forms have now 
been cultivated by Noguchi in anaerobic 
cultures of defibrinated patient's blood in 
ascitic fluid agar to which fresh tissue has 
been added. They breed true to type. 
The spirochetes may be transformed to 
Fig. 121.— Spirochete ober- m ; ce an( j m0 nkevs. Thev are numerous in 

meien in the blood (von 1 1 • 1 » i 

Jaksch). the blood during the fever, but rapidly dis- 

appear at the crises, due to the presence of 
a spirochetolytic substance in the blood. Immune bodies also appear 
and can be used to impart passive immunity to other animals. 

Pathological Anatomy. — The spleen becomes greatly enlarged; it 
frequently presents a variegated appearance on section, due to areas of 
anemic infarction and necrosis, or fatty degeneration alternating with 
deeply congested portions. The spirochetes can be found in this organ, 
particularly in cells. The lymphatic tissues are swollen throughout 
the body. 

Pathological Physiology. — The peculiar feature of relapsing fever, 
the one that has given it its name, is the recurring paroxysms of 
fever. The cause of this periodicity is as yet unknown, though it is 
likely that the development of the spirochete is such as to determine 
the relapses. 



VINCENT'S ANGINA 



This is an acute infectious, pseudomembranous and ulcerative form of 
pharyngitis and tonsillitis giving a grayish or greenish exudate, The 
process below the membrane is usually necrotizing and spreading, and 
may persist for a long time. There are constitutional symptoms and 
involvement of the regional lymph-glands. The organism of the dis- 
ease is found in two forms, the Bacillus fusiformis and the Spirillum 
vincenti. They are believed to be two forms of the same organism, as 
the spiral has been said to grow from the rod. The rod is irregularly 
staining and pointed, 3 to 12 n long by 0.3 to 0.8 /x wide. The spiral 
is long, wavy, uniformly staining, flexible, and has pointed ends. The 
rod forms spores. The organisms are anaerobic, growing best upon 
ascitic fluid agar, on which they appear as minute gray colonies. Gas 
is formed in glucose media. Cultures have a fetid odor. The patho- 
genesis of the organism for lower animals is practically nil ; no immunity 
reactions are known (Fig. 122). 



DISEASES DUE TO BACTERIA 



341 




Fig. 122. — The fusiform rods and spirilla of Vincent's angina. Smear direct from throat. 

FRAMBESIA OR YAWS 

This is a tropical disease resembling syphilis in its primary indurated 
sore and secondary rash, caused by a spirochete (Spirochoeta pertenui 
Castellani), similar to the Spirochceta pallida. The eruption is yellow- 
ish, papular, covered with crusts, and consists histologically of epi- 
thelial hyperplasia, in the form of papillomatous growths or extensions 
downward, associated with increase of leukocytes, plasma, and eosino- 
phile cells. The diseaseJ^nds-teward recovery, except in children and 
debilitated persons. The productive character of the lesions is not so 
marked as in lues. The disease has been transmitted to monkeys. 

\ 

Diseases Due to Higher Bacteria 
actinomycosis 

Definition. — A tinomycosis is a chronic infectious process char- 
acterized by inflammatory reaction of the tissues with a tendency to 
the formation of suppurative foci, and due to the specific action of a 
micro-organism, the Actinoviyces bovis. 

Etiology. — Actinomycosis is a disease of cattle, horses, swine, 
sheep, the llama, the elephant, deer, dog, and occasionally of man. 

The specific cause of the disease is an organism which occurs in 
the tissues in the form of clusters having a radiate structure, and it has, 
therefore, been termed the "ray fungus." These clusters may be so 
small as to be invisible to the naked eye, or they may reach considerable 
dimensions by their growth and aggregation. The central part of the 



342 A TEXT-BOOK OF PATHOLOGY 



cluster frequently has a granular appearance, suggesting a mass of micro- 
cocci. Reaching out from this may be seen more or less regularly diverg- 
ing strise or rays, and the periphery is composed of what appear to be 
bulbous extremities of the rays (Fig. 123). 

Bostroem, in 1890, and Wolff and Israel, in 1891, published notable 
articles on actinomycosis and respectively isolated an aerobic and an 
anaerobic growth. The relation of the former to actinomycosis has, 
however, been disproved, while the anaerobic growth alone is important. 

The aerobe of Bostroem was ap- 
parently a contaminating organism 
related to the branching organisms 
which occur in the outer world, and 
that have been variously classified 
as streptothrix, cladothrix, etc. As 
these occur on various grains and 
on the spears of the oat seed, etc., 
Bostroem believed that the organ- 
ism was derived from such sources. 
More recently accurate studies like 
those of Wright {Jour. Med. Re- 
search, May, 1905) seem to have dis- 
proved the, connection of the aerobic 
organism and to have established 
the independence of the true actino- 
myces from the group of branching 
organisms referred to. Wright insists that these should be classified 
as a separate genus under the name of Nocardia. 

Cultivation of the Organism. — Growths have been obtained upon 
sugar-agar, in bouillon, and various other media. Suspension cul- 
tures in dextrose or glucose sugar show in the course of two to four 
days scattered colonies in the depth of the agar and a very few within 
5 to 10 mm. of the surface. A shallow zone of closely set colonies 
giving the appearance of a dense cloudiness in the media and about 
2 to 4 mm. wide is generally found at a point about 5 to 10 mm. below 
the surface. Below this zone the colonies are more scattered. 

The growths are essentially anaerobic, and grow best at body tem- 
perature. Under the microscope the smaller colonies are found to be 
spherical masses of branching filaments radiating from the center. 
The branching is true branching and increases as the colony grows older. 

In stab-cultures in sugar-agar the growth appears as a dense gray 
streak or line of small nodules in the deeper parts of the stab. No 
growth occurs near the surface. 

In bouillon, solid white masses form at the bottom of the tube; none 
appear near the surface. In bouillon the growths occur both under 
aerobic and anaerobic conditions, but in the case of the former Wright 
suggests that on account of the compactness of the masses there are 
really anaerobic conditions within the colony. 

While this anaerobic organism may be the most important one in 




DISEASES DUE TO BACTERIA 



343 



actinomycosis, an aerobic growth has been cultivated, and it seems that 
both forms may cause the disease. 

The cultivation of these organisms presents unusual difficulties, owing 
chiefly to the frequent presence of other bacteria in the lesions, which 
usually grow more rapidly and more luxuriantly than does the specific 
organism. 

In a few cases pure cultures were obtained by planting the granules 
directly in bouillon. In some instances of contamination, by allowing 
the tube to stand for several days, the contaminating organisms died 
out and transplants then yielded pure cultures. Generally sugar-agar 
was the medium employed for isolation of the micro-organism. It 
grew well only in agar and bouillon cultures and in the incubator at 37° C. 
(98.6° F.). In the other usual cultural media and at room temperature 
it grew very poorly or not at all. It was essentially an anaerobe, and did 
not form spore-like reproductive elements. In cultures its colonies 
were similar in character to those in the lesions. The vitality of the 
micro-organism was variable. In general, it did not seem to survive as 
long in cultures as when dried on the sides of test-tubes. It was killed 
by exposure to a temperature of from 60° to 64° C. (140°-147.2° F.) for 
ten minutes. The micro-organism stained well by Gram's method, the 
clubs losing the stain and taking the contrast stain; it is not acid fast to 
Gabbet's decolorizing solution after staining with carbol-fuchsin. 

The filaments of colonies immersed in animal fluids, such as blood- 
serum and serous pleuritic fluid, may under certain unknown conditions 
become invested with a layer of hyaline eosin-staining material of vary- 
ing thickness and the filament may then disappear. Thus structures 
are produced that seem to be identical with the characteristic "clubs" 
of actinomyces colonies in the lesions. 

Pathogenicity. — Inoculation experiments on animals with cultures 
of the micro-organism result in producing in the tissues of the inocu- 
lated animal characteristic "club"-bearing colonies. This club forma- 
tion Wright is inclined to believe represents a kind of protective mem- 
brane for the mass of the colony against the destructive action of 
the juices and cells of the tissue. After the inoculation of animals 
nodular lesions and in some instances relatively extensive lesions were 
produced. They, however, showed little tendency to progress and only 
in a few cases did multiplication of the organism in the body of the 
animal seem probable. In other words, these results simulate closely 
the negative or ambiguous results obtained by other observers who 
inoculated animals with the lesions of actinomycosis. It would seem, 
therefore, probable that the micro-organism in the cultures was identical 
with the micro-organism in the lesions. 

Wright recognized but one micro-organism as the characteristic in- 
fectious agent in typical actinomycosis, and applies to it the generic 
and specific name of Actinomyces bovis, as given by Bollinger and Harz. 
There is not sufficient difference between the actinomyces from the 
human and bovine cases to justify their classification as separate species. 

The manner of infection with the actinomyces is not completely 



344 



A TEXT-BOOK OF PATHOLOGY 



determined. Formerly it was thought that the parasite was carried to 
the tissues by various vegetable substances, particularly the spears of 
the oat-seed and other grains. Sometimes these have been found 
embedded in the lesions; in other cases splinters of wood have been 
discovered. The fact that the organism prefers anaerobiosis and grows 




Fig. 124. — Actinomycosis of the jaw-bone of an ox. The dark areas and the broken-down 
part in the center of the picture are foci of the disease. The whole bone is enlarged. 

only at body temperature tends to disprove this view, and it is likely 
that the actinomyces is a normal inhabitant of the mouth and gastro- 
intestinal tract and always derived from these sources, although, of 
course, infection by infected grain or communication with infected 
animals or persons can transmit the disease. Carious teeth and lesions 
of the mucous membranes may play a part in the etiology. 



DISEASES DUE TO BACTERIA 



345 



Pathological Anatomy. — The pathological changes induced by 
the actinomyces consist of round-celled infiltration and proliferative 
changes in the connective tissue surrounding the parasite, and some- 
times secondary softening, necrosis, or suppuration. The granulation 
tissue of actinomycosis is especially rich in leukocytes, and not infre- 
quently these form dense foci, which later develop purulent collections. 
In cattle the disease affects the lower jaw, less frequently the upper jaw 
or other bones; the tissues of the neck, the tongue, and other parts. 
In man it is met with in the gums, the cheeks, and floor of the mouth; 
in the lungs, intestines, and other internal organs. The naked-eye 
appearance of the lesions may first be simply that of a hard red papular 
formation, with more or less induration surrounding it; later this tends 
to increase in size and may break down, forming necrotic or suppurative 
excavations. The process of repair or cicatrization may proceed in 
some parts to the extent of almost complete repair, while the suppura- 
tive or necrotic change advances in other directions, and thus cavities 
and irregular communicating sinuses are established. The part in which 
the disease exists may be considerably disfigured and much enlarged. 
The pus or necrotic material within the lesions contains peculiar granular 
bodies, the "sulphur granules" or actinomycosis bodies. The sand-like or 
sulphur granules measure 0.2 to 0.6 to at times 1.2 mm. They are of a 
gray, yellow, green, to red color; when young, soft; when older, much 
tougher in consistency. Occasionally calcification of the diseased area 
may take place. When the jaw-bone is affected the disease, as a rule, 
begins about carious teeth, fistula? communicating with the roots of teeth 
(Fig. 124). 

In the case of disease of the lungs some have observed a preliminary 
catarrhal inflammation of the bronchi. More frequently, however, 
there are from the first nodular areas of bronchopneumonia, which 
tend to undergo changes similar to those already described. The sur- 
rounding lung tissue frequently becomes indurated from interstitial 
pneumonitis. Extension may occur to the pleura, pericardium, and 
mediastinal tissues. 

In the case of actinomycosis of the intestinal tract there are first 
elevations of the mucous membrane, the disease involving the mucosa 
and the submucosa. Subsequent softening of these leads to the forma- 
tion of ulcerations. Extension to the peritoneum and to the other organs 
of the abdomen may take place. 

In any case of actinomycosis a penetration of the blood-vessels or 
lymph-channels may lead to metastases. Thus in actinomycosis of 
the abdominal cavity the liver is frequently involved; and other parts 
of the body may be similarly affected. Actinomycotic lesions of the 
brain (abscesses) are sometimes seen in such instances. In other cases 
of cerebral involvement there may be no evidence of the original focus 
or point of entrance of the germ. 

Microscopically, the characteristic feature of this disease is the 
parasite itself surrounded by lymphoid cells in considerable numbers, 
with some epithelioid cells and occasionally giant cells. When the 



346 



A TEXT-BOOK OF PATHOLOGY 



process tends to a favorable termination by cicatrization, fibrous-tissue 
formation proceeds in the usual manner. 

Pathological Physiology. — The actinomyces is mainly active as a 
local parasite, the general disturbances of health being comparatively 
slight. There is a marked tendency to limitation or retardation of the 
disease, and sometimes this is effected completely. 

MYCETOMA 

Mycetoma, or madura-foot, is an infectious disease occurring in 
India and elsewhere, and probably caused by several organisms, cer- 
tainly two, grouped under the name Streptothri.v or Actinomyces 
madurcE. Babes asserts that the black variety is due to a mucor or asper- 

gillus. The disease is not infrequent in 
Madura, Delhi, and other parts of India, 
and has been observed in Africa, south- 
ern Europe, and America. 

Etiology and Pathological An= 
atomy. — As its name indicates, the dis- 
ease affects the foot, and usually follows 
injuries, particularly thorn wounds. In 
rare cases the hands or other parts are 
affected. At first there is nodular in- 
flammatory swelling, beginning on the 
plantar surface or dorsum of the foot 
and spreading to the sides. These swell- 
ings are hard and painless. Later, soft- 
ening occurs and rupture takes place. 
Thin, watery pus is discharged, and 
this contains grayish or reddish granular 
bodies or black granules resembling par- 
ticles of gunpowder. In the former 
case the term "pale mycetoma" is ap- 
plied; the latter variety is called black 
or melanoid. In the later stages of the 
disease discharging sinuses may remain, 
while newer nodules, in turn, are formed 
and soften. Finally, the member af- 
fected becomes greatly deformed, the portions not involved growing 
thin, while the diseased part increases in size. Death occurs from ex- 
haustion or complications. 

Histologically, the nodules resemble large tubercles, but are highly 
vascular. The bulk of the growth consists of granulation tissue cells, 
those in the center being small, those near the outer edge often large and 
containing two or more nuclei. True giant cells are rare. In the center 
may be found a branching micro-organism, called Streptothrir madurce 
(Vincent). This stains by Gram's method, and sometimes shows some- 
what bulbous swelling of the ends of the threads and their branches 
(Fig. 125). The mycelia of the black variety of mycetoma are described 




Fig. 125. — Streptothrix madurse 
in a section of diseased tissue (Vin- 
cent). 



DISEASES DUE TO BACTERIA 



347 



by Laveran as thicker and coarser than those of the pale form, and he 
believes the organisms are of a distinct variety or species. Around the 
organism may be seen an area of degeneration, having a striate arrange- 
ment suggesting that seen in actinomycosis. Extensive degeneration and 
pus formation occur in the center of the diseased areas in the later 
stages; and hemorrhage may occur from the new blood-vessels. Histo- 
logical examination of the granules in the pus shows the micro-organisms 
in the form of interlacing threads. Bodies resembling spores have 
occasionally been described. 

The organism has not as yet been definitely classified. It is cer- 
tainly allied with the actinomyces, but probably not identical. It has 
been cultivated upon various media, particularly infusions of hay and 
the like, rendered slightly acid in reaction. It forms small nodular and 
hard growths, which become rose-red in color when they cling to the 
sides of the test-tube near the surface of the liquid, or brownish when 
they sink to the bottom. Upon agar isolated grayish or, later, rose-red 
clusters are formed. Inoculation experiments have thus far met with 
little success. Local reaction has been so produced, but not a definite 
disease. Several investigators have reached the conclusion that there 
are two or more kinds of micro-organisms that have an etiological relation 
to cases of Madura foot. It has in particular been suggested that the 
white and black varieties of the disease have a distinct bacteriology. 
These views need further confirmation. 

THRUSH 

This condition occurs in newborn infants and in older children 
or adults who have become weakened by disease. The organism called 
Oiduun albicans is a budding fungus, 
though some believe it a form of 
mould. If some of the milky de- 
posits on the mucous membrane of 
the mouth which characterize the dis- 
ease be removed and examined mi- 
croscopically, mycelial threads and 
conidia are observed. The organ- 
ism may be cultivated upon gelatin 
plates, in the form of whitish colonies 
on the surface, or granules with radi- 
ating processes in the depth of the 
medium. On potato and on bread 
it forms a white coating. The organ- 
ism is present in the air and in vari- 
ous articles of food, so that infection 
readily takes place. 

The organisms first grow upon the surface of the mucosa, but later 
may penetrate to considerable depth, and may attack blood-vessels. 
If this occurs, metastasis may result, with abscesses in different organs, 
notably brain and kidney. 




Fig. 126. — Thrush fungus (Endomyces 
albicans) (Kolle and Wassermann). 



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A TEXT-BOOK OF PATHOLOGY 



SACCHAROMYCOSIS OR BLASTOMYCOSIS 

This is a subacute infection, chiefly of the skin, caused by forms of 
yeast, Saccharomyces hominis or S. busse. There are probably several 
different species capable of setting up infection, but their action is 
essentially the same. Saccharomyces tumefaciens and Blastomyces 
dermatitidis are also names given to yeasts causing disease in the skin. 

The yeast is a rounded or elongated (up to 30 jj), doubly contoured, 
highly refractile body, with vacuolated, granular or clear cytoplasm; 
multiplication occurs by budding. The organisms are best stained by 
polychrome methods. They grow with difficulty and require carbo- 
hydrates. They are most easily obtained by inoculating guinea-pigs 
under the skin and culturing the pus. They produce an active cellular 




Fig. 127. — Blastomyces in pneumonic exudate (from a photograph by Dr. S. S. Kneass). 

exudate in which fibrin is abundant. Necrosis is common. A toxin of 
moderate potency is produced. The lesions are said to be primarily 
cutaneous or pulmonary, although some question the latter. The 
spread is probably hematogenic, as scattered abscesses and osteomye- 
litis may occur. The lesion is usually a mixture of suppuration and 
granulation tissue (see p. 148). The disease may be transferred to the 
lower animals. No immunity reactions are of value. 

Coccidiosis, or Oidiomycosis, is an acute infection due to the Coccid- 
ioides immitis, an organism closely related to the Oi'dia, and has some of 
the characters of both the classes, Blastomyces and Hyphomyces. It is 
a doubly refractile circular body in the tissue, occasionally growing 
out into mycelia, and always doing this in cultures. It develops by 
intracellular sporulation and not by budding. The infection usually 



DISEASES DUE TO BACTERIA 



349 



has its seat in the skin, but may become generalized. The lesion 
resembles a tubercle in the cellular and degenerative characters. Eosin- 
ophiles may be present. 

Sporothricosis. — This is a disease consisting of cutaneous eruptions 
and multiple abscesses, usually in the skin, but not infrequently in the 
mucous membranes, muscles, tendons, and mammary gland. It is caused 
by the Sporothri.v beurmannii, after the investigator who first accurately 
described it. The organism appears in several slightly different varie- 
ties. It occurs in lesions as round or oval yeast-like bodies, but on 
cultivation shows long mycelial threads from which grow yeast-like 
spores or gonidia. The spore body measures 3 to 6 by 2 to 4 /x. In the 
tissues usually only the yeast-like stage is seen, but short mycelia may 
form. The organism is aerobic and requires the presence of carbohy- 
drate for its growth. The disease is subacute. In addition to the 
above-mentioned lesions, the mould may produce a nodular lymph- 
angitis in man as it can in the lower animals. A disseminated form with 
the moulds in the blood is reported and considered a grave condition. 
The disease is transmissible to the lower animals. The blood contains 
an agglutinin and a complement-fixing body against the mould. For 
histology of the lesions, see p. 149. 

Dermatomycosis. — Besides the above infections, there are several 
moulds which infest the skin and produce more or less specific reactions 
of clinical rather than pathological importance. The following skin 
diseases are included under this heading: Favus, caused by Achorion 
schdnleinii; ringworm, including Tinea tonsurans, Tinea sycosis, Tinea 
circinata, and Tinea versicolor, due to varieties of the genus of moulds 
Trichophyton. The moulds infest the epidermis or penetrate the gland 
ducts. Their action is to cause the epithelium to degenerate and 
desquamate, while a round and polynuclear cell invasion occurs in the 
dermis. There is little specificity pathologically. 

Granuloma pyogenicum, or human botryomycosis, is a granulating 
pyogenic and ulcerative condition of the dermis, penetrating to the sur- 
face, said by some to be due to bacteria, but lately ascribed by others 
to an intracellular protozoon-like body. 

Other Bacteria Not Causing Specific Infection 
the hemorrhagic diseases 

These diseases constitute a group of affections of probably quite 
divergent character, which, however, are similar in presenting hemor- 
rhages in and from the mucous membranes, in the skin, serous sur- 
faces, and in the deeper tissues or organs. 

The general causes of hemorrhage must be considered in connection 
with these diseases. Among the causes capable of producing hemor- 
rhages such as occur in the hemorrhagic diseases are mechanical coiidi- 
tions, as atheroma or other diseases of the walls of the blood-vessels; 
toxic conditions, such as poisoning by the venom of animals and by 
various blood-poisons, and probably obscure poisons produced in the 



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A TEXT-BOOK OF PATHOLOGY 



course of anemia or other diseases; infectious conditions, such as occur 
in hemorrhagic variola, scarlatina, etc.; and nervous conditions, as are 
illustrated in the hemorrhages following injuries to the brain and those 
accompanying certain states of cerebral excitation. 

Clinically, the hemorrhagic diseases or purpuras may be classified 
as primary and secondary, the former occurring without any definite 
preceding disease; the latter being symptomatic of various disorders. 
Among the primary there are: (1) infectious forms, including, with 
more or less probability, purpura, scurvy, and various forms of crypto- 
genetic sepsis; (2) toxic forms, as those due to drugs and venom of ani- 
mals; (3) mechanical forms, as, perhaps, hemophilia, to the extent that 
vascular weakness may be a factor. Among the secondary purpuras 
are: (1) infectious forms, as scarlatina, variola and the like; (2) mechan- 
ical forms, as those due to cardiac and arterial diseases, or embolism; 
(3) toxic forms, as those resulting from intestinal auto-intoxications, 
jaundice, pernicious anemia, etc.; and (4) nervous forms, as those due 
to hysteria, diseases of the brain, etc. 

The underlying conditions in cases of infection whose most im- 
portant manifestation is hemorrhage are to be sought first in the blood- 
vessels and then in the blood. In the former case the poison has a dele- 
terious effect upon the permeability of the blood-vessels, while in the 
latter hemolysis occurs in the blood-stream; thus escape is easy. It is 
probable that the two actions are to be found in all hemorrhagic con- 
ditions. 

The infectious purpuras interest us particularly in the present place. 
Various micro-organisms have been found in different forms of hemor- 
rhagic disease. Kolb described a bacillus pathogenic for animals which 
occurred in 5 cases of hemorrhagic purpura. Babes and Oprescu isolated 
a bacillus from one case of hemorrhagic septicemia, and others have 
found various micrococci, especially the streptococcus. It is not un- 
likely that various micro-organisms may assume a peculiar virulence 
and acquire the power to produce hemorrhages under certain circum- 
stances. 

Some recent investigations seem to indicate that scurvy is a tox- 
emia due to poisons generated in preserved meat foods as a result of 
autolysis. In scurvy, however, several micro-organisms have been 
described, but the one which has the best claim for consideration is 
that discovered by Babes, a delicate bacillus occurring in the gums. 
Streptococci were found in association with it. Some Japanese investi- 
gators have recently claimed to have discovered a specific bacillus in 
the blood and viscera, agglutinable by the serum of scorbutic patients. 
Present indications, however, do not very strongly substantiate the 
probability of a bacterial cause for this disease. 

PROTEUS INFECTION 

The Bacillus proteus and its several subvarieties occur in decom- 
posing animal matter and in association with necrotic and gangrenous 



DISEASES DUE TO BACTERIA 



351 



processes in the living body. The organism is a small, motile bacillus, 
occurring in pairs and less often in chain formations. It is abun- 
dantly supplied with flagella. 

Cultivation and Demonstration. — The organism grows very well at 
ordinary temperatures, and forms characteristic growths on gelatin- 
plates. At first yellowish colonies with outgrowths are formed; the 
gelatin liquefies, and the outgrowths move about in a tortuous manner 
and become separated from the original growth. Peculiar figures 
are formed, and the term Bacillus figurans has been applied. The cul- 
tures have a putrid odor. The organism is readily stained with ordinary 
solutions like carbol-fuchsin. 

Pathogenicity. — Injected intravenously in animals, hemorrhagic 
vomiting and diarrhea result. In man the bacillus has been found asso- 
ciated with phlegmonous inflammations, gangrenous processes, cystitis, 
pyelitis, and in infectious icterus (Weil's disease). It is sometimes the 
cause of meat poisoning. 

infectious diseases whose cause is not certainly known. 
Filterable Viruses 

yellow fever 

Definition. — Yellow fever, or typhus icteroides, is now recognized 
as infectious and transmissible through the bite of a certain form of 
mosquito, the Stegomyia fasciata or calopus. The specific organism has 
not been identified. 

Etiology. — Many different organisms have been described as the 
cause of yellow fever, most prominent of them being the Bacillus 
icteroides of Sanarelli. It seems now that none of the many is of any 
importance whatever, as the disease is transmitted by mosquitoes in 
which no bacillary form of infective agent has been found, and because 
the virus is filterable. 

The Role of Mosquitoes. — The experiments of Reed, Carroll, and 
Agramonte demonstrated the importance of mosquitoes as agents 
in the transmission of the disease. It was definitely proved by Reed 
and his associates that a special form of mosquito, the Stegomyia 
fasciata, carries the contagion from one person to another. The germ 
must pass a certain incubation period in the body of the mosquito, as 
the bite of the latter is not found to cause infection until after an inter- 
val of twelve days or more from the time it has fed on the yellow-fever 
patient. A bite at an earlier period after contamination did not confer 
immunity against a subsequent attack of the disease. This indicates 
that a cycle of development must occur in the mosquito. Without the 
Stegomyia fasciata there can be no yellow fever, as there can be no malaria 
without Anopheles. The mosquito must feed on a yellow-fever patient 
during the first three days of the fever, and after the twelve-day period 
is infective for at least fifty-seven days. The spread of the disease is 
checked by preventing the mosquito from biting patients or by its whole- 



352 



A TEXT-BOOK OF PATHOLOGY 



sale destruction. The blood of patients is infective even after passage 
through a Berkefeld filter. One attack confers immunity. Experiments 
were conducted directly on non-immune volunteers, and the transmissi- 
bility of the disease was positively proved. The incubation period 
of the disease, the time elapsing from the time of the mosquito's bite up 
to the first definite symptoms, varied from forty-one hours to five days 
and seventeen hours. The results of the practical measures of quaran- 
tine instituted at Havana in accordance with Reed's work — destruction 
of all mosquitoes and careful exclusion of mosquitoes from the patients, 
with entire disregard of clothing, bedding, etc. — show that the disease 
is not directly contagious. Non-immune nurses attend yellow-fever 
patients with impunity. The disease can also be transmitted experi- 
mentally by subcutaneous injections of blood taken from patients in the 
first and second days of the disease, which proves the presence of the 
parasite, in the blood at least, in the earlier stages of the disease. The 
passage of the parasite through an intermediary host is, therefore, not 
essential. In this respect yellow fever resembles malaria. 

Pathological Anatomy. — The lesions of this disease are mainly 
those of the internal organs — liver and kidneys. In the liver extensive 
fatty degeneration leads to swelling and light color of the organ, and 
on section there may be a mottled appearance due to the alternation 
of healthy and fatty areas. In the kidneys degenerative changes of the 
parenchyma and extravasation of blood are associated in varying pro- 
portions. The appearance may be that of an acute hemorrhagic nephri- 
tis or, more particularly, that of degenerative nephritis. Hemorrhages 
in the mucous and serous surfaces are frequent, particularly extravasa- 
tions in the mucosa of the stomach. 

Pathological Physiology. — The organism of yellow fever probably 
produces abundant toxin. 

MEASLES 1 

Measles, or rubeola, is an infectious and contagious disease, in 
all probability due to some micro-organism. A number of micro- 
organisms have been described. Several observers (Canon and Pielicke, 
Czajkewski) have found a bacillus somewhat resembling that of in- 
fluenza; others have found bacilli resembling the pseudodiphtheria bacil- 

1 Certain investigators have discovered bodies having some of the appearances of 
protozoa in measles, scarlet fever, pernicious anemia, leukemia, sarcomata of various 
sorts, and in a number of other diseases. These observations, however, do not merit 
further discussion in this place. Future investigations must decide whether they have 
been accurate or not. 

Mallory {Jour. Med. Res., January, 1904) found in the skin of 4 cases of scarlet fever, 
dying in the early stages of the disease, certain bodies which in their morphology suggest 
that they may be various stages in the developmental cycle of a protozoon. They were 
found once in small numbers in the epidermis of the tongue. They were not present 
in the skin of 6 cases dying in the early stages of the disease, nor in a number examined 
in the desquamative stage. They occur in and between the epithelial cells of the epidermis, 
and free in the superficial lymph-vessels and spaces of the corium. 

There are in addition to these forms larger coarsely reticulated forms which may 
represent stages in sporogony or degenerations of the other forms. 

The name Cyclasterion scarlatinale has been proposed by Mallory for this organism. 
These and other protozoon-like bodies, such as described by Doehle, Ross, and others, are 
now considered by many writers as belonging to the Chlamydozoa. 



DISEASES DUE TO BACTERIA 



353 



lus, but the bacteriology is still unsettled. Doehle described a protozoan 
organism occurring in the blood. Hektoen has inoculated healthy per- 
sons with the blood from cases of measles and has demonstrated the 
transmissibility. 

The disease is at present regarded as due to an ultramicroscopic virus 
which will pass through a porcelain filter. The virus is present in the 
blood, buccal and nasal secretions, and can be transmitted to monkeys, 
in which it produces an atypical infection. It may be found in the blood 
before the Koplik spots or eruption appear. It has not been cultivated. 

Mild catarrhal inflammations of the faucial, nasal, and conjunctival 
membranes and of the bronchial mucosa are customary lesions. With 
these conditions is associated some congestive and inflammatory enlarge- 
ment of the regional lymphatic glands. In severe cases pseudomem- 
branous inflammations of the throat are sometimes met with, and 
bronchopneumonia and parenchymatous nephritis are occasional 
complications. The eruption of the skin is the visible evidence of a 
moderate dermal and subdermal inflammation. Focal necroses of the 
liver have been described. Many of the lesions are doubtless caused by 
secondary infections. 

SCARLET FEVER 

Scarlet fever, or scarlatina, is an infectious and contagious disease 
probably due to a micro-organism. A variety of organisms have been 
discovered in cases of scarlet fever, but none as yet has proved to be 
specific. Among other bacteria the pyogenic micrococci (streptococci) 
have been regarded as etiological agents. This, however, is by no means 
established. Protozoan organisms have also been described (Doehle). 
Mallory has described under the name of Cyclasterion scarlatinale 1 
structures which present the appearance of protozoa. 

The virus is now believed to be filterable and ultramicroscopical. 
An atypical infection is produced in monkeys by injection of a patient's 
blood during the height of the attack. The claim that scarlatina is due 
to streptococci or to the leukocyte inclusion bodies of Doehle cannot be 
substantiated. 

Lesions of the mucous membranes and glands similar to those of 
measles, but usually more intense, are generally present. Suppuration 
of the glands of the neck is a possible termination, and severe inflam- 
mations of the throat, middle ear, larynx, and trachea, with endo- 
carditis or pericarditis, are much more frequent than in measles. Many 
of these complicating conditions are caused by secondary infection with 
the Streptococcus pyogenes. Diphtheria (as contrasted with streptococcic 
lesions of the throat presenting a similar appearance) is not rare as a 
complication. Parenchymatous nephritis is a lesion of great clinical 
interest, while focal necroses of various organs are observed in fatal 
cases. 

1 See note, page 352. 



23 



354 



A TEXT-BOOK OF PATHOLOGY 



MUMPS 

The bacteriology of mumps is uncertain. Charrin and Capitan 
isolated a number of organisms, mainly micrococci and motile bacilli. 
A number of other authors subsequently obtained similarly indefinite 
results. Laveran and Catrin in 1893 found a diplococcus. 

The pathology of mumps is that of an acute inflammation of the 
parotid or submaxillary gland. This rarely terminates in suppuration 
or, on recovery, in induration of the gland. 

VARIOLA AND VACCINIA 

A number of bacteria have been described from time to time in 
these diseases, and various micrococci in particular have been found 
in the pustules, but none of these can be considered as specific. Several 
bacilli, one form resembling the diphtheria bacillus, have been recently 
described. 

In 1887 Pfeiffer and van der Loeff independently described a proto- 
zoan parasite of the order Sporozoa, which occurs in the cells of the rete. 
This organism was found in variola as well as in vaccinia. Pfeiffer, 
Guarnieri, and other investigators found that by inoculation of the 
cornea of rabbits large numbers of the supposed parasites make their 
appearance in the epithelial cells. These organisms are rounded bodies 
lying in the protoplasm of the cells, sometimes singly, sometimes in 
groups of two or three. Slow ameboid movements are visible and the 
organisms present one or more nuclei. Spore formation has been ob- 
served by several investigators. Guarnieri suggested the name Cytoryctes 
varioloe seu vaccina. 

Councilman, Magrath, and Brinckerhoff in 1903 confirmed the find- 
ings of Guarnieri in 1892 and of Wasielewski some years later as to cell 
inclusions in lesions of vaccinia and variola. They look upon them as 
living organisms and the probable etiological factor of vaccinia and 
variola. In vaccinia the cytoryctes occurs as a structureless mass in 
the cytoplasm, where it is thought to undergo asexual division by break- 
ing up into small round segments. In variola the parasite is said to 
invade the nucleus also, undergoing there segmentation into ring-like 
bodies; this is supposed to be the sexual phase. 

The formation of the exanthem may be due to the infected endo- 
thelial cells of the capillaries or lymph-spaces being carried to the skin 
capillaries by the blood-current. No differential method of staining has 
as yet been offered. The nature and significance of these supposed 
organisms have not yet been positively determined. Some authorities, 
as Ewing, look upon them as products of cell degeneration. Lately 
the view has been defended that they are the Chlamydozoa of Prowaczek, 
probably due to a virus acting upon the chromatin, with lysis thereof. 

Secondary infections with various micrococci or other organisms 
are common in small-pox and vaccination, and may play an important 
part in pustulation, and in the more definite complications, such as 



DISEASES DUE TO BACTERIA 



355 



septicemia, pneumonia, hemorrhagic septicemia, erysipelas, and the 
like. 

Councilman, in discussing the relations of variola vera, vaccinia, and 
variola inoculata, points out that vaccinia differs from small-pox in 
three ways: first, the period of incubation is shorter, being five days 
in man and three days in calves, while that of variola is twelve days. 
Second, in vaccinia the general eruption is absent. Third, for the de- 
velopment of vaccinia the virus must be placed in contact with a suscep- 
tible epithelial surface, and cannot be carried by the air. 

In his studies of 52 autopsies careful study was made to determine 
the existence of a primary variolus pustule from which the general 
infection might have occurred. None was found, nor are there any 
symptoms of such a primary lesion. Nevertheless, a simple pox, in the 
lungs, for instance, might occasion no distinctive signs. He believes that 
the infection passes through the air and enters the system through the 
lungs. The virus is filterable through porcelain in diluted condition. 

Regarding immunity conferred by vaccination, he states that all 
the evidence goes to show that it is due to germicidal power of the 
blood-serum which enables the serum to destroy the virus of vaccinia 
and small-pox. 

VARICELLA 

The etiology of chicken-pox is even less definitely determined than 
that of small-pox. Pfeiffer discovered the same organism described by 
him in vaccinia and variola. Bacteria of one sort or another have been 
occasionally found. 

TYPHUS FEVER 

An acute epidemic disease attended with a fairly typical clinical 
course and macular eruption, supposed to be transmitted by the louse, 
Pediculus vestamenti. The virus is found best in the blood toward 
the end of the disease, is filterable, and may be transmitted to monkeys. 
Many different organisms have been discovered and described, but 
none are now believed to be the real cause. The organism now receiv- 
ing most attention is a non-motile rod with a palely staining central 
area, circulating in the blood. It is said to grow feebly under anaerobic 
conditions if cultures are made between the sixth and ninth day of the 
attack. It will act as an antigen in the complement fixation series. 

The severe typhus of Mexico is called "tabardillo." There is a mild 
infection called "Brill's disease," after the observer, believed to be a 
sporadic form of typhus. It has been observed among the Hebrews 
of New York and other American cities. 

The lesions of typhus fever suggest an intense infection and in- 
toxication. The blood is often dark-colored and rapidly putrifies. 
Various organs, such as the liver, kidneys, and heart, show pronounced 
cloudy swelling or fatty degeneration of the cells. The spleen is notably 
enlarged, often quite soft, and may present infarctions due to thrombus 
formation. 



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A TEXT-BOOK OF PATHOLOGY 



Inflammations of the mucous membranes, especially bronchitis, 
pharyngitis, and laryngitis, are common, and pneumonia is a frequent 
result. 

RABIES 

Etiology. — We have every reason to believe that rabies is due to a 
specific germ. In 1903 Negri described an organism which has received 
considerable recognition as the probable specific cause of the disease. 
The "Negri bodies" have been found in the large nerve-cells of the 
central nervous system, especially in the cornua ammonis, in various 
animals and human beings affected with rabies. They are absent in 
other conditions. In early stages of the disease the bodies are sparsely 
present and are exceedingly minute structureless spherules lying in the 
protoplasm of the nerve-cells. Later the bodies increase in number and 
size and contain one or more darkly staining granules. Stained by the 
Nocht-Romanowsky method the bodies are robin-egg blue, the granules 
darker in color. 

Virus. — In rabic animals the virus is found principally in the saliva 
and in the central nervous system. It is occasionally known to pass into 
other organs, such as the lacrimal gland and the pancreas. It is never 
found in the blood or in the liver, spleen, kidney, or the muscle tissues. 
The contents of the stomach may contain it, owing to the swallowing of 
the saliva. It affects principally the central nervous system, and is 
found in the most concentrated form in the medulla oblongata. The 
virus may be present in the saliva for at least three days before the 
animal shows any, symptoms of madness, and it may be present eight 
days before any symptoms appear. It may be present in the central 
nervous system two days before the appearance of any symptoms. The 
symptoms do not show themselves until the poison or virus has remained 
in the nervous tissue long enough to produce structural and functional 
change. After it is introduced into the body it undoubtedly "multiplies 
itself" during the period of incubation. It is a "solid body," as it may be 
removed from the saliva by filtration through porcelain. There is, 
however, almost undoubtedly a stage of development of the virus when 
it is small enough to pass through porcelain. An emulsion of brain of 
an infected dog will give a filtrate infective for rabbits. It is found 
in human milk, tears, aqueous humor, and cerebrospinal fluid. The 
virus penetrates to the nervous system by following the nerve-trunks 
from the site of injury to the spinal cord. This has been proved by com- 
parison of portions of the cord and of the nerves at varying periods after 
inoculation. The virus is destroyed by drying and by the action of 
light. 

Noguchi has lately demonstrated that the virus of rabies may be 
cultivated upon anaerobic serum-cultures. It takes the form of minute 
masses of chromatin surrounded by a clear zone and a membrane, and as 
very minute granular and somewhat coarser pleomorphic chromatoid 
bodies. The former multiply by budding and division and suggest 



DISEASES DUE TO BACTERIA 



357 



protozoa. Similar pictures may be found by dark-field examination of 
hydrophobia brains. The bodies are from 1 to 12 jx across. 

The loss of virulence by drying is gradual and regular; hence this is 
taken advantage of for the production of "vaccine." The virus is com- 
pletely destroyed at a temperature of 50° C. (122° F.) in one hour. It 
remains uninjured by exposure to extremes of cold — 10 or 20 degrees 
below zero. 

The Danger from Bites. — The richer the nerve-supply, the greater the 
danger, and punctures are more dangerous than lacerated wounds. 
The wolf, the cat, and the dog, in the order named, are the most dan- 
gerous animals. 

Period of Incubation. — Man, forty days; cats, fourteen to twenty- 
eight days; dogs, twenty-one to forty days. Other animals vary from 
fourteen to fifty-six days. 

The Season. — More frequent during the period from April to Sep- 
tember than any other part of the year. 

Preventive Inoculation. — Pasteur devised a method of treatment 
which consists essentially in successive inoculations with emulsions of 
spinal cords of increasing virulence. The virulence of the material used 
for the first inoculations is decreased by drying the cords for varying 
periods, and the injections are begun with the older cords and continued 
with increasingly virulent material. 

Pseudohydrophobia or Lyssophobia. — This is simply a condition of 
fright, and the patients invariably recover. 

Pathology. — Gross Appearances in Organs. — There is no gross lesion 
that can be considered specific of the disease. The cadavers are apt to 
be emaciated and to become putrid rapidly. The blood is usually dark 
and thick. The brain and the membranes may be congested, and may 
even show slight hemorrhages. The gastro-intestinal tract and the 
respiratory tract may be congested and also show slight hemorrhages. 
Rabid dogs frequently swallow wood, straw, stones, and the like, which 
are found in the stomach postmortem. 

Microscopical Appearance. — There is nothing distinctive outside of 
the nervous system. Changes are found in the ganglia of the cerebro- 
spinal and sympathetic systems, and are especially marked in the 
plexiform ganglion of the pneumogastric nerve and in the Gasserian 
ganglion. Normally, these ganglia are composed of supporting tissue 
holding in its meshes the nerve-cells. These nerve-cells are surrounded 
by an endothelial layer and capsule. The rabic virus brings about 
an abundant multiplication of the cells lining this capsule, leading 
finally to the destruction of the normal ganglion, and leaving in its 
place a collection of round cells. All ganglion cells are not markedly 
changed; some are slightly or not at all changed; others are entirely 
destroyed. These changes are particularly marked in the dog, less so 
in man, and still less so in the rabbit. The ganglion of the pneumo- 
gastric nerve is the one generally chosen for examination, and it should 
be removed immediately after death and placed in absolute alcohol 
or in formalin solution. 



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A TEXT-BOOK OF PATHOLOGY 



RHEUMATISM 

Definition. — Acute articular rheumatism is probably an infectious 
condition; the nature of the infectious agent, however, is uncertain. 

Etiology. — The manifestations of rheumatism agree very well with 
those of infectious diseases, and some of the lesions frequently com- 
plicating the disease, such as endocarditis, are invariably infective. 
The relationship between tonsillitis andj rheumatism has been ex- 
plained by some as that between primary and secondary disorder. 
It is supposed that the infectious agents effect an entrance into the 
body through the tonsils, causing primary tonsillitis and secondary 
general infection, with localization in the joints. In other cases it has 
been held that the organisms enter through abrasions of the skin or in 
other ways. 

Leyden and others have described a streptococcus, and it has been 
shown that this organism is capable of producing arthritis, endocar- 
ditis, and pericarditis in experimental animals. A considerable number 
of recent investigators have isolated a micrococcus or streptococcus 
from cases of rheumatism and have succeeded in producing joint lesions, 
endocarditis, and pericarditis in animals inoculated with it. Others, 
however, have produced similar lesions with streptococci from other 
sources. 

The organism now receiving most attention is the Streptococcus 
rheumaticus of Poynton and Paine. This is a hemolytic acidifying 
diplococcus requiring blood for its best cultivation. It has been found 
in synovial fluids and tissues, in the blood, and in heart-valve vegeta- 
tions. It is suggestively like the chorea micrococcus. It produces 
arthritis and endocarditis in experimental animals. 

Achalme described a bacillus which he and others found in a number 
of cases of acute articular rheumatism. It is a large bacillus resembling 
that of anthrax; sometimes it is motile; it stains well with anilin dyes 
and with Gram's stain; may have a capsule, and forms polar spores 
much larger than the bacillus. This organism is obligate-anaerobic, 
growing best in liquid media, in which it forms small bubbles of gas. 
The organism is closely allied to or identical with Welch's Bacillus 
aerogenes. Thioroloix claims to have produced typical symptoms in 
the rabbit; and the inoculation experiments of others have given sug- 
gestive results. This bacillus was obtained from the blood in a number 
of cases; and from the pericardial fluid and blood in a state of purity in 
one case. The organisms have been found in sections of the heart muscle 
and valves. 

The fact that one organism or another produces inflammatory 
lesions in the joints, endocardium, or pericardium of animals when 
injected intravenously does not prove a specific relation of the organism 
to rheumatism. Doubtless various organisms are capable of producing 
such lesions, and it is not improbable that the clinical disease rheuma- 
tism may include a variety of infections. 

(For the pathological anatomy of rheumatism, see Diseases of the 
Joints.) 



DISEASES DUE TO BACTERIA 



359 



BERIBERI 

Definition. — Beriberi, or kakke, is an epidemic or endemic specific 
polyneuritis, with alterations of sensation and motility, and associated 
disturbances of digestion. This disease was long regarded as an infec- 
tion, and in some particulars strongly suggests an infection, but is of 
uncertain etiology. It occurs in tropical and subtropical countries, 
and is characterized by muscular weakness, generalized muscle pains, 
dropsy, and cardiac failure. 

Etiology. — Beriberi occurs among young persons and usually affects 
numbers of people. It is most frequent along ocean coasts and great rivers, 
and is most prevalent during damp seasons of the year. It does not seem 
to be contagious. Dietary conditions, such as may arise from defective 
food on ships and in institutions, appear important in its etiology. 

The cause of beriberi is unknown; no virus has been isolated to 
establish its infective nature, and it is now believed to lie in certain 
foods, notably, rice and canned meats, of which the former is the more 
important. In milling and polishing rice, the pericarp, rich in valuable 
phosphorus, is removed. Much information has been gleaned by the 
experimental production of a degenerative peripheral neuritis in birds 
by feeding with such polished rice, and a similar experiment has been 
made with condemned prisoners. The importance of the unknown 
substance in the covering of the rice grain is shown by the fact that 
improvement follows the use of rice-bran in beriberi and experimental 
polyneuritis. This substance is either necessary to nutrition, or its 
absence disturbs metabolism in the nervous tissues. Some observers 
believe toxins are formed by cooking improperly preserved or spoiled 
rice. Moszkowski produced beriberi in himself by a diet of polished rice. 
His symptoms indicated no change in the motor nerves, the sensory only 
being affected, and the reflexes were increased. There was excessive 
nitrogen excretion, but the phosphorus metabolism seemed normal. 
The disease may be transmitted to the young through the milk. The 
form chiefly associated with superficial dropsies is called "kakke," be- 
lieved by some to be an independent disease. This is denied by others. 

The sensory phenomena take the form of areas of reduced tactile 
sense and are commonly met upon the dorsum of the foot, finger-tips 
and dorsum of the hand, around the mouth, and upon the abdomen. 
Edema of the superficial parts may or may not be seen. Then follow 
palsies of the dorsal muscles of leg and hand, and at times of the cranial 
nerves supplying face and neck. Death occurs by exhaustion or 
intercurrent infections. The pathology, except in the nervous system, 
is in no way specific. There is a slight anemia and leukocytosis. Edema 
in several isolated areas may be found. Congestions and early inflam- 
mations are common. This is particularly true of the gastro-intestinal 
tract, where the mucosa is cyanotic, but the glands are little if any 
changed. Parenchymatous degenerations are met. In the peripheral 
nerves there is degenerative neuritis with increase of nuclei, probably 
from the sheath of Schwann. The ganglia on the posterior roots and 
occasionally the roots themselves are degenerated. 



360 



A TEXT-BOOK OF PATHOLOGY 



PELLAGRA 

This is a chronic, relapsing, non-febrile disease characterized by a 
more or less specific cutaneous eruption and nervous and digestive dis- 
turbances. Its etiology is not certainly known, but it has been supposed 
to be due to the use as food of Indian corn in which a toxin has arisen 
by infestation with certain aspergillus species. This is in accord with 
its appearance in the spring and summer. Various bacilli and amebse 
have been considered causes of pellagra, and lately Sambon asserts 
that it is transmitted by an insect. Late observations indicate that it 
may be transmitted to monkeys by Berkefeld filtrates from tissues of 
human cases. It occurs most commonly in white females between 
twenty and forty, beginning in May and June. Poor environment and 
living conditions favor its development. 

The cutaneous manifestations take the form of an erythematous 
dermatitis on exposed parts, which are aggravated by exposure to sun- 
light. The skin may swell or vesicles may form. The distribution is 
apt to be symmetrical and the patches limited. Thickening of the super- 
ficial layers, with pigmentation and parchment-like appearance, is the 
common condition in later stages. 

The nervous conditions comprise anesthesias, paresthesias, early 
increase of reflexes, and tremors. Later, evidences of dementia set in. 

There is no specific pathology. There are congestion and pig- 
mentation, and sometimes fatty degeneration of parenchymatous 
organs. Ulcers in the colon may be found. In the nervous system 
meningitis of a low order, degeneration of a few nerve- and ganglion 
cells, perivascular infiltration of round cells and degeneration of the 
posterior and lateral columns have been reported. The cerebrospinal 
fluid is usually abundant, possibly under pressure, limpid, clear, sterile, 
and contains some increase in protein and lymphocytes. 

There seems to be a lowered and somewhat perverted protein 
metabolism in pellagra. Judging from the known facts that hyper- 
acidity exists in the stomach, we may assume that digestion is defi- 
cient in the intestine. 

The microscopical changes in the skin are degeneration in the corium, 
followed by mild granulation tissue and thickening accompanied by 
proliferation in the spinous and granular epithelium in which pigment 
is prominent. 

The last two diseases, beriberi and pellagra, seem to be due to the 
absence from the diet of substances necessary to the construction of the 
phosphatids of nervous tissue, to which Funk has given the name 
"vitamins." Their exact nature is not yet clear, but they do not seem 
to be proteins or carbohydrates. 

DENGUE 

This is an acute infection common in the tropics, due to a filterable 
virus, transmitted by the mosquito Culex fatigans. The virus is in the 
blood. There are fever, with an intermission, rheumatoid pains, and 
varied skin eruptions. One attack gives no immunity. 



DISEASES DUE TO BACTERIA 



361 



POLIOMYELITIS 

This disease of the central nervous system has assumed a position 
of great interest during the past decade, for during that time it has been 
pandemic, at least in Europe and North America. It was formerly 
known as a sporadic disease of childhood, but its recent manifestations 
have been those of a transmissible epidemic disease affecting almost 
any age, though especially frequent in childhood. 

The infection begins with a mild febrile attack, to which is shortly 
added muscular and joint pains, followed by palsy, and later by distinct 
paralysis. (For the pathology of the disease, see Nervous System.) 

Etiology. — The exact nature of the causative agent of this disease is 
not yet certainly known, but Noguchi has lately been able to cultivate 
from the central nervous system a tiny, poorly staining, bacterium-like 
body, with cultures of which he claims to be able to produce the disease 
in monkeys. Not only has this observer been able to grow these bodies, 
but he has found them in sections of nervous tissue. 

While little is as yet known of this tiny bacterium, much has been 
learned of the distribution and behavior of the virus. It is to be found 
in the brain, spinal cord, ganglia, spinal fluid, nasal mucosa, lymphatic 
organs, and intestinal contents. If emulsions of parts containing the 
virus be injected into the brain of a monkey the animal will develop 
symptoms, signs, and the pathology of poliomyelitis. If, instead of 
the emulsion, a filtrate of it, through a Berkefeld filter, be used, infection 
will also result; the virus is, therefore, filterable. Heating to 50° C. 
(122° F.) one-half hour destroys the virus, but it will withstand drying, 
50 per cent, glycerin, and tissue autolysis. The virus is said to be con- 
stantly in the nasal secretions of infected persons, sometimes in those of 
attendants, and also in surroundings, notably in dust. 

Transmission. — Two theories are proposed for the transmission of 
poliomyelitis: first, that it is spread by insects; and, second, that con- 
tact, direct or indirect, is responsible. 

The insect transmission theory is based upon the appearance of the 
disease usually in summer, and upon the discovery by Rosenau that it 
was possible to transmit the disease from monkey to monkey by the 
bite of the stable fly (Stomoxys calcitrans) . 

The contact infection theory is based upon the fact that the virus 
is present upon and in the nasal mucosa of patients and healthy attend- 
ants. The latter are suspected of being carriers. Much more impor- 
tant than these, however, are the so-called "abortive" cases of polio- 
myelitis. These are instances in which only a mild febrile affection 
occurs, but which do not go on to palsies, or, at most, show only 
transient weakness; therefore, so atypical that they escape recognition, 
and, going abroad, actively disseminate the virus. 

The nose as a portal of entry gains somewhat in probability when one 
considers the short distance the virus has to travel to reach the central 
nervous system by passing along the olfactory tract. 

Immunity. — One attack of poliomyelitis, either natural or experi- 



362 



A TEXT-BOOK OF PATHOLOGY 



mental, gives immunity, but this immunized power cannot be trans- 
ferred to another individual. As yet no therapeutically valuable anti- 
serum has been found. The serum of an immune person or animal 
does, however, possess the power to neutralize the virus. If such a 
serum and a known virus be mixed, incubated, and injected into a mon- 
key, no paralysis will occur, while a control animal injected with the 
same virus not exposed to the immune serum will develop poliomyelitis. 
This test has made it possible to detect abortive cases, because no unin- 
fected person gives serum with this property. 

FOOT-AND-MOUTH DISEASE 

This infection of cattle may be transmitted to human beings who 
use milk from affected cows, or directly from infected animals. There 
is a vesicular eruption in the mouth and on the feet and hands com- 
parable to the lesions in cows. The virus is in the vesicular fluid; 
it has not been cultivated, but is filterable. One attack probably 
gives no immunity; the blood-serum has therapeutic and preventive 
properties. 

TRACHOMA 

This is a transmissible disease of the conjunctiva characterized by 
tiny granulations on the palpebral surfaces, said by some to be due to 
an invisible filterable virus; by others it is believed to be caused by an 
influenza-like bacterium. Some observers have found an intracellular 
body which they believe to be the cause. This has been placed among 
Prowaczek's Chlamydozoa. (See chapter on Eye.) 

ROCKY MOUNTAIN FEVER 

This is an acute transmissible disease characterized by evidences of 
general infection, severe pains, and a macular or erythematous erup- 
tion. It is transmitted by the tick Dermacentor occidental is. It is practi- 
cally confined to the Rocky Mountain States and is most frequent and 
severe in Montana. It is a disease of adult life, occurring chiefly among 
those who work abroad, and is prevalent in summer. The tick obtains 
the virus by blood-sucking, and transmits it to another person by biting. 
The female tick transmits it to the eggs and young. The virus is in the 
blood of the patient and is destroyed if this be heated to 50° C. (122° F.) 
or is dried ; it will not pass a Berkef eld filter. The disease may be trans- 
mitted by the introduction of infected blood into a guinea-pig, rabbit, 
or horse, and the clinical course in these animals is closely comparable 
to that seen in man. The serum of experimentally infected animals 
has an immunizing value for other animals, but it possesses little if any 
therapeutic power. It has been claimed that there is in the infected 
blood and ticks a minute diplococcoid body resembling an organism of 
the hemorrhagic septicemia group. No bacteriological cultivation has 
been successful, so that the cause of the disease is not known. One 
attack, in the laboratory animals at least, confers immunity. 



DISEASES DUE TO BACTERIA 



363 



THE CHLAMYDOZOA 

This is a name given by v. Prowaczek to certain intracellular bodies 
whose zoological position is not clear, but which have some characters 
suggestive of the protozoa. They undergo a change in appearance 
which has been interpreted by some observers as a metamorphosis. 
No exact life cycle has been accepted by all authorities as certainly 
pointing to protozoal nature. The group includes the Negri bodies of 
rabies, the cytoryctes of vaccinia and variola, the cyclasterion of 
scarlet fever, the trachoma bodies, etc. Prowaczek and his followers 
interpret these chlamydozoa as the result of cellular infestation by 
ultramicroscopical bodies, in response to which the nucleus or nucleolus 
extrudes into the cytoplasm some of its material. The intracellular body 
seems at first to be either a clear space or a minute dot until it is sur- 
rounded by the chromatin material as above derived. The chlamydozoon 
then assumes the form of an irregular mass of chromatin with one or 
more clear spaces. It appears in any imaginable form, giving the im- 
pression of metamorphosis. Cytoplasm seems to form, but if this be 
de novo or only a part of altered cell protoplasm is not known. The 
virus causing these protozoon-like changes within the cell is filterable, 
associated with colloids, and has a predilection for epiblastic tissues. 
No chlamydozoon is known apart from the cell manifestation, and 
none has been cultivated. 



CHAPTER X 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 

PROTOZOA 

Classification. 1 — Class I. Rhizopoda (Sarcodina) , forms resembling the ameba, 
and characterized especially by the presence of pseudopods. 

Class II. Flagellata (Mastigophora) , protozoa characterized by the presence 
of one or more long lash-like flagella, used for progression or acquirement of food. 

Class III. Sporozoa, forms living as parasites in the tissues of other animals, 
receiving their food only by osmosis. Reproduction by means of encysted spores. 

Class IV. Infusoria (Ciliata), cell-body of fixed shape with cilia; living free 
in water or as parasites. 

Class V. Suctoria, cell-body provided with suctorial tubes. Usually ecto- 
parasites in water animals and plants. 

The protozoa differ from the bacteria in producing a progressive 
disease without evidences of immunity. Trypanosome infection shows 
the presence of some immune bodies in the blood, but any increase of 
antiprotozoal power of the serum does not seem to limit the course 
of disease, nor can the serum be used to immunize another person. 

Some of the protozoa produce a toxin, but most of them exert their 
noxious power by mechanical injury or obstruction, acting with the 
products of tissue destruction or with bacteria. Protozoa do not as a 
class have a pronounced chemotactic power for leukocytes. They pro- 
duce proteolytic enzymes and their activity is followed by an increase of 
acid in their vicinity. 

Most protozoa have tissues of predilection, such as malaria Plas- 
modia, the blood; amebse, the colon and liver; sarcosporidia, the 
muscles. 

Rhizopoda 
entamoeba histolytica 

Description. — This organism is an ameboid body from 20 to 30 ju in 
diameter, consisting of a clear protoplasmic refractive outer portion and 
a finely or coarsely granular protoplasm within (Fig. 128). It frequently 
shows vacuoles and sometimes a vesicular nucleus. It presents active 
ameboid movements when studied on a warm stage of the microscope; 
and frequently contains foreign bodies, such as bacteria, pigment-par- 
ticles, and portions of blood-corpuscles or other cells. 

In the movements of the organism pseudopodia are projected from 
some part of the periphery. These at first draw upon the clear periph- 
eral zone, but after their formation the granuloplasm flows into the 
projected pseudopods. When in unfavorable surroundings the organ- 

1 Braun, Die tierischen Parasiten des Menschen, 1903. 

364 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 365 

ism undergoes a form of change called the encysted state. In this the 
body becomes spherical, and the wall is eventually stiff and firm, and 
usually presents a double contour. The division into a clear and a 
granular protoplasm is lost, the organism being uniformly granular. 




Fig. 128. — Entamoeba histolytica. Living organisms. Note absence of nucleus. 
All three of the parasites contain red blood-corpuscles; X 750 (Bulletin No. 1, Medical 
Department U. S. Army, 1913). 

Schaudinn differentiates two forms of the dysentery amebae, calling 
them Entamoeba histolytica (Fig. 128) and Entamoeba tetragena (Fig. 




Fig. 129. — Entamoeba tetragena. Living specimens. Note nucleus in upper enta- 
meba. The three lower entamebse contain red blood-corpuscles; x 750 (Bulletin No. 1, 
Medical Department U. S. Army, 1913). 

129). Craig and others now consider them to be different stages of 
development of the same species, but this opinion is not held by all 
parasitologists. 



366 



A TEXT-BOOK OF PATHOLOGY 



Distribution and Pathogenesis. — The organism in question has 
been found abundantly in the stools of patients suffering from dysentery. 
It is readily detected in the necrotic particles or the mucus of the stools, 
and has also been found in the tissues of the bowel wall adjacent to the 
dysenteric ulcers and in the liver abscesses secondary to dysentery. 

Liver abscess is a frequent complication or sequel of amebic 'dys- 
entery. The protozoa reach the liver through the blood-stream, prob- 
ably by penetrating radicles of the mesenteric vein, and are found in 
the wall of the abscesses. Whether they alone can produce pus is not 
known. There may be abscesses elsewhere. 

Musgrave and Clegg have cultivated amebse with cultures of bac- 
teria, and should a colony grow free of bacteria it may be kept alive 
for a short time on an agar media to which extracts of tissue have been 
added. The injection of mucus containing the amebse into the rectum 
of cats and other animals has occasionally produced typical dysentery, 
but this does not prove the pathogenicity of the amebse. Lesions 
closely similar to the natural disease have been produced in monkeys, 
and a human case with very suggestive clinical course was caused by 
swallowing capsules containing amebse. The Entamceba histolytica 
produces a moderately strong poison which causes cellular necrosis, 
but not much acute inflammation. 

ENTAMCEBA COLI 

This smaller ameba (10 to 20 tx in diameter), also differing from 
the Entamoeba histolytica in having a less greenish color, less distinct ec- 
toplasm and endoplasm, less distinct pseudopodia, in the usual absence 
of vacuoles, the almost invariable presence of a nucleus and well-defined 
nuclear membrane, and in rarely ingesting red corpuscles, has been 
found in the feces of from 50 to 70 per cent, of healthy persons in various 
localities. Possibly under certain conditions the ameba may become 
pathogenic; usually it has been found in persons entirely well. 

OTHER AMEBiE 

Several other amebse of lesser importance have been discovered. 
Among these are the Entamoeba urinalis, found in the urine in cases of 
cystitis, and several forms met with in the mouth, especially about 
the teeth. Entamoeba buccalis has lately been held responsible for 
pyorrhoea alveolaris. An ameboid organism of uncertain pathogenic 
significance has been discovered in the abdominal fluid of cases of ascites. 
It has been named Leydenia gemmipara. It has a pulsating vacuole 
and nucleus and multiplies by budding or division. 

MASTIGOPHORA {Flagdlala) 

CERCOMONAS HOMINIS 

This organism is a pear-shaped body with a sharp anterior extremity 
provided with a delicate short cilium. The broader posterior end is 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 367 

provided with a long, tail-like flagellum. A large and a small variety 
have been described (Fig. 130). The former is the variety usually found 
and is from 10 to 12 /x in length. A minute oval aperture has been 
found at the anterior extremity. 

Significance. — The organism has been discovered in great numbers in 
various diarrheal conditions, especially in cholera. It has, however, 

A B 

Fig. 130. — Cercomonas hominis: A, large; B, small, variety (Davaine). 

been found in the stools of from 10 to 25 per cent, of healthy persons 
in tropical countries and is not known to have definite pathogenic 
powers. It is not improbable that the organism is, in reality, a form of 
trichomonas. 

Other closely allied cercomonads have been found in the urine 
(Bodo urinarius, Cercomonas urinarius). 

CERCOMONAS COLI HOMINIS 

A single observation of this organism was made by May. The 
body of the parasite was not quite the size of a red corpuscle; rather 
granular and glistening and slightly greenish. It was spindle shaped, the 
anterior end more blunt than the posterior. Four cilia were found at- 
tached to this end, and upon one side of the organism was seen an 
undulating membrane. In the same case smaller bodies, less developed 
and probably younger parasites, were discovered. The patient suffered 
from carcinoma of the stomach and chronic diarrhea. 

TRICHOMONAS INTESTINALIS 

This organism is pear shaped; from 10 to 15 fx in length and 7 /x in 
breadth (Fig. 131). The anterior end is blunt; the posterior end is 




Fig. 131. — Trichomonas intestinalis (Zenker). 

prolonged into a sharp, tail-like projection. The body is granular and 
contains one or two bodies resembling vacuoles. Near the anterior end 
at one side may be seen a row of ten or twelve cilia, which give the or- 
ganism active motility. It has also ameboid movements. 

Significance. — This organism has been found in cases of diarrhea, but 
its significance is doubtful. 



368 



A TEXT-BOOK OF PATHOLOGY 



TRICHOMONAS VAGINALIS 



This form is rather smaller than the last, with an attenuated caudal 
end and a more blunt anterior portion, provided with three or four 
flagella; there is a lateral undulating membrane with six or seven short 
cilia. 

Significance. — The organism has been found in cases of vaginitis 
due to various causes, but also in the vagina in the absence of evident 
disease. 

It has been claimed by some writers that the four forms of flagellates 
just described are, in reality, but variants of a single species or inaccur- 
ately described members of the same variety. They accompany some 
forms of amebse. Their most important pathological seat is the bladder, 
where they can set up an irritation. 



Sternberg has found several forms in the mouth, and especially 
about the teeth. These have been termed Trichomonas flagellata, 
T. caudata, and T. elongata. A trichomonas closely related to Tricho- 
monas vaginalis has been found in gangrene of the lung and in putrid 
bronchitis. 



This organism in its active state is irregularly pear shaped, and 
presents at its broad end a cup-shaped depression situated obliquely at 



Figs. 132 and 133. — Lamblia intestinalis from the intestines of a mouse (Grassi and 

Schewiakoff ) . 

one side (Figs. 132 and 133). On the anterior edge of the depression are 
attached two long cilia, and at one point of the posterior lip are two pairs 



OTHER FORMS OF TRICHOMONAS 



LAMBLIA INTESTINALIS 




Fig. 132. 



Fig. 133. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 369 

of cilia. In the base of the depression are seen two vesicular structures 
(nuclei) united by a band. The protoplasm is finely granular and is sur- 
rounded by a delicate capsule. When free the organism is capable of 
rather rapid motion, but in the intestine it is attached to the epithelial 
cells by its cup-shaped depression. The organism exists in this form 
in the duodenum and jejunum. In the colon or other unfavorable situ- 
ations it forms oval encysted bodies showing the nuclei and cilia within. 

Significance. — Lamblia is a frequent parasite of the mouse, but has 
been found in the intestines of other animals, and occasionally in man. 
It has been found especially in chronic diarrheal conditions, and at 
times appears in the stools in immense numbers. No definite lesions 
have been found, and the pathogenicity of the germ is uncertain. 

TRYPANOSOMA 

Several varieties of trypanosomes have been recognized in animals, 
notably in horses and cattle. Among these, Trypanosoma evansi (Steel) 
has been found in the disease "surra" in horses and mules in India 
and Burmah; the T. brucei (Plimmer and Bradford) has been found in 
"nagana," a disease of horses and cattle in Central Africa; a form prob- 
ably identical with T. brucei has been found in "mal de Caderas," a 
disease similar to surra and nagana in Central South Africa and Brazil; 
T. equiperdum (Doflein) or T. rougeti (Laveran) in the disease of horses 
known as "dourine" in Algeria and other countries. A comparatively 
harmless variety ( T. lewisi, Kent) occurs in a large proportion of wild 
rats. It has been the form on which many of the studies of trypano- 
somes have been made. A few other forms have been recognized. 

The trypanosome was discovered in the blood of a human patient 
by Dutton. The earlier reported cases of Nepvieu are open to some 
doubt. Dutton's patient, an Englishman, had been along the Gambia 
River, and his symptoms were much the same as those met with in 
animals from the same parasitic invasion. Great wasting and weakness, 
especially in the legs; irregular relapsing fever; edema, especially about 
the eyes; injection of the skin and conjunctivae; enlargement and 
tenderness of the spleen, and frequent pulse and respirations, were the 
principal symptoms. Castellani announced in 1902 his discovery that 
the sleeping fever of the African negro is caused by a variety of trypano- 
some. 

The name Trypanosoma gambiense (Dutton) has been proposed for 
the parasite of man (Fig. 134). 

The trypanosome is a minute, worm-like body, difficult to see in 
the fresh blood with a magnification of 300 diameters. One end of the 
parasite is drawn out into a flagellum; the other end is bluntly conical. 
An undulating membrane is attached along the body, which is short, 
thick, and granular. Near the posterior end is found a refractile spot 
(vacuole). The parasite moves forward or backward by means of the 
flagellum, but usually toward the direction of the flagellated end. 
Reproduction occurs by longitudinal fission, and, in addition, it is 

24 



370 



A TEXT-BOOK OF PATHOLOGY 



thought, can occur by sexual reproduction. The organism readily dies 
in fresh preparations. In the stained preparation it was found 18 to 
25 fx in length and from 2 to 2.8 ju in width. 

Novy and McNeal succeeded in cultivating trypanosomes in arti- 
ficial media composed of 1 part of nutrient agar and 2 parts of fresh 
defibrinated or laked rabbit or rat blood. The organisms retain their 
virulence in cultures for long periods of time. 

The trypanosome of man has been found pathogenic for certain 
monkeys and for dogs, cats, and rats. 

Transmission of the Disease. — The transmission of the parasite is 
effected by various blood-sucking flies. The Trypanosoma gambiense is 
conveyed by the Glossina palpalis; T. brucei, mainly by the tsetse fly, 
G. morsitans; T. lewisi, by fleas. The fly conveying the human para- 
site acts as a host, for it becomes infective three days after biting, and 
remains so four weeks, thus indicating that some form of metamorphosis 
takes place. 




Fig. 134. — Trypanosoma gambiense: (1) From the blood; (2) from serosanguinolent 
fluid; (3) form showing rounded posterior extremity and granular protoplasm; (4) dividing 
form; X about 2000 (Laveran and Mesnil). 

The organism may exist in the blood of man for a long time without 
causing symptoms. Later it enters the cerebrospinal fluid and then 
causes the characteristic manifestations. As a rule, there is first irregu- 
lar fever, later pains and swelling of the extremities, and finally coma. 

The lesions discovered at autopsy consist of cerebrospinal meningeal 
congestion with increased fluid, and enlargement of the spleen and liver. 
The cerebrospinal fluid is in excess and cloudy, but not purulent. The 
arachnoid may be lifted from the convolutions and the pia has been 
found abnormally tight. The lymph-nodes are almost universally 
enlarged and the spleen frequently shows a myeloid transformation. 

Immunization of animals has been accomplished by repeated in- 
oculations and immune sera of decided potency have been produced. 

Human trypanosomiasis is transmissible to monkeys. 

Leishmaniosis. — This term may be given to a group of three dis- 
eases prevalent in Africa and Southern Asia, known as "kala-azar" or 
"dumdum fever," "infantile kala-azar," and "oriental sore" or "Aleppo 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 371 



button." The causative organism is a near relative of the trypano- 
somes, among the Flagellata. The symptoms of the first two are 
moderate anemia and fever, associated with splenomegaly. The 
spleen shows little microscopical change aside from hyperplasia. The 
prognosis is grave. Oriental sore is characterized by the appearance 
on skin surfaces of spreading suppurating and ulcerating granulomata. 
These lesions tend to heal and leave disfiguring scars. 

The causative organism is known as Leishmania donovani, after the 
men who discovered and described it. It varies but slightly in the 
three clinical forms above, only differing in size and appearance upon 
cultivation. It may be grown upon the medium described for trypano- 
somes. In the body the parasite exists as an intracellular round or 
oval (2.5 by 3.5 fi) mass containing two more deeply staining large 
granules. The larger, or nucleus, lies excentrically, parallel to the 




Fig. 135. — Leishmania donovani. Flagellated forms from a culture. Wright's stain; 
X 1800 (Bulletin No. 1, Office of the Surgeon General, January, 1913). 

long axis of the parasite. The smaller granule is probably the blepharo- 
blast. Vacuoles may be present. The parasites stain palely, while 
the granules are dark. They lie within lymphocytes and endothelial 
cells. They do not appear in any numbers in the circulating blood, 
but may be found in lymph-tissue and marrow (Fig. 135). 

The manner of transmission is not known, but insects and bedbugs 
are suspected. 

Histoplasmosis is a condition characterized by anemia, prostration, 
splenomegaly, fever, and emaciation, caused by the Histoplasma capsvr 
latum (Darling), a flagellate related to the trypanosomes. The organs 
may occasion spreading granulomata and the intestines show ulcera- 
tion. The organism is intracellular, has an irregular oval nucleus, 
vacuoles, and a wide capsule. The organism has not been cultivated. 
The disease was found in the Panama Canal Zone. 



372 



A TEXT-BOOK OF PATHOLOGY 



HEMOSPORIDIA 
THE PARASITES OF MALARIA 

The organisms which are now recognized as the cause of malaria 
belong to the protozoa. Most authors regard them as Sporozoa, 
suborder Hemosporidia. They are found in the blood and the vascular 
channels of the various organs, deriving their nourishment, for the 
most part, directly from the blood-corpuscles. 

Malaria has been regarded as a water-borne and as an air-borne 
disease, but no proofs have been obtained for either view. Direct conta- 
gion does not occur, but it has been shown that the blood is infectious 
when introduced into the circulation of a healthy person. The drinking 
of the blood does not give rise to the disease. Certain external condi- 




Fig. 136. — Plasmodium vivax. Half- 
grown parasite. Wright's stain; X 1500 
(Craig, Bulletin No. 6, War Department). 



Fig. 136a. — Plasmodium malaria?. 
Half-grown parasite, the so-called band 
form. Wright's stain; X 1800 (Craig, 
Bulletin No. 6, War Department). 



tions are favorable or necessary to the development of the disease. 
These external conditions are moist, marshy soil, atmospheric humidity, 
and high temperature. The disease occurs in the lowlands or bottom- 
lands, and very rarely in high and dry ground. Extensive excavations 
and the like may cause the appearance of the disease or increase it, 
and, on the other hand, suitable drainage may cause its diminution or 
disappearance. The relation of all these conditions to malaria is ex- 
plained by the demonstration of the part played by mosquitoes in the 
transmission of the contagion. 

Three distinct species have been identified: the organism of tertian 
fever (Plasmodium vivax, Figs. 136-138), that of quartan fever (P. 
malaria'), and that of estivo-autumnal fever (P. falciparum). Each 
of these has a double life cycle, one within the human host, the other 
in the body of the mosquito. In the human circulation, spleen, or else- 
where asexual reproduction (schizogony) of the parasite occurs until it 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 373 



has exhausted its reproductive power or antagonistic bodies have de- 
stroyed it; while in the mosquito sexual reproduction (sporogony) 
occurs by conjugation. 

Plasmodium Vivax. — The cycle of development in the blood of man 
begins with a small hyaline spherule (schizont) about 2 ju in diameter 
which is attached to and later within a red corpuscle. Soon pigment 
particles appear within the parasite, being derived from altered hemo- 
globin. The pigment particles are more or less actively motile, due to 
currents in the protoplasm. Later the body increases in size and the 
corpuscle in which it is contained swells and becomes paler. Finally, 
the sphere increases to perhaps twice the size of a normal corpuscle. 
In all stages ameboid changes in the shape of the organism may be 
observed, but become less and less marked as the plasmodium enlarges. 
In the spleen, and to a less extent in the circulating blood, division of the 




Fig. 137. — Plasmodium vivax. Fully de- Fig. 138. — Plasmodium vivax. Fully de- 
veloped macrogametocyte. Wright's stain; veloped microgametocyte. Wright's stain; 
X 1800 (Bulletin No. 1, Medical Depart- X 1800 (Bulletin No. 1, Medical Depart 
ment U. S. Army, 1913.) ment U. S. Army, 1913). 



parasite may be observed about the time of the expected paroxysm of 
the disease. The pigment collects in the center, the organism forms 
a rosette and then divides into fifteen or twenty rounded segments or 
merozoites. These escape from the destroyed red corpuscle and are then 
ready to attack a new corpuscle and begin the same cycle. 

In the earlier stages the hyaline body appears as a light area on an 
otherwise normal red corpuscle; somewhat later its rounded shape sug- 
gests a ring and the term "ring-bodies" is given. This is conspicuous 
in preparations stained with a chromatin stain such as in the Nocht- 
Romanowsky method. The body of the parasite is blue and at one 
point in the periphery may be seen red chromatin matter, thus suggest- 
ing a signet ring. Before segmentation the chromatin collects in the 
center and eventually divides, a portion being found in each of the 
merozoites. The cycle of development of this form occupies about forty- 
eight hours. 



374 



A TEXT-BOOK OF PATHOLOGY 



Plasmodium M alarm. — The organism of quartan fever differs 
from the tertian in that it is less pigmented and the pigment is usually 
coarser, more characteristically arranged at the periphery of the para- 
site, and usually motionless. The segmentation is more regular, forming 
a wheel-like figure with nine to twelve segments which form the sporules 
or merozoites. The segmentation occurs only in the circulating blood 
and the cycle occupies seventy-two hours. The corpuscle containing 
the organism does not enlarge nor grow pale as in the case of the ter- 
tian form, but instead presents a greenish appearance. 

Plasmodium Falciparum. — The organism of estivo-autumnal fever 
is believed by Italian and tropical investigators to occur in two forms: 
a tertian and quotidian, which have certain distinguishing features. 
The organism is characterized by its tendency to develop marked 
signet-ring forms, by its relatively small size, and by its fine granulation 
and highly refractive protoplasm. Segmentation occurs in forty-eight 
hours and takes place mainly in the spleen, bone-marrow, liver, and 
capillaries of the brain. The segments are from seven to ten in number. 

Sporogony. — A certain number of the plasmodia of any one of the 
three varieties, when of mature size, instead of undergoing segmenta- 
tion become differentiated as male and female forms or gametocytes. 
In the tertian and quartan varieties the male form, or microgametocyte, 
is a rounded body with centrally placed nucleus, having an abundance 
of chromatin and a considerable amount of actively motile and diffused 
pigment matter (Fig. 138). The macrogametocyte, or female form, has an 
excentrically placed nucleus with less chromatin and coarser pigment 
arranged in clumps about the periphery of the organism (Fig. 137). In 
the case of the estivo-autumnal parasite the gametocytes first appear as 
oval bodies within the red corpuscles, but soon they assume the well-known 
form of crescents, which even when quite mature may present on the 
concave border remains of the red cell in which they developed. The 
crescent contains rod-shaped pigment in a cluster either at its center or 
one pole, and a male and female form can be distinguished. These 
sexual forms (gametocytes) of malarial plasmodia are less abundant 
in the earlier stages of infection than later when schizogony or asexual 
division becomes less active. 

When blood is drawn and kept for a time under a cover-glass further 
changes take place in the gametocytes, which are similar to those which 
occur in the body of the mosquito. The microgametocyte presents 
active movements of its pigment and finally a protrusion of several 
flagella which extend to two or three times the diameter of the cell. 
These flagella, or microgametes, the male element concerned in the process 
of fertilization, become detached from the cell and penetrate the female 
organism, macrogametocyte, after the latter has undergone a prepara- 
tory change (certain nuclear extrusions) and has thus been converted 
into a macrogamete. Further stages in the sexual cycle of reproduction 
occur only in the body of the mosquito. 

Parthenogenesis. — It has been claimed by Schaudinn, but denied by 
others, that parthenogenesis of the macrogametocyte may restore to the 



PLATE 2 



3 

V* fit 



■ft?...: V 



// /<? 

— r(.. 

«r~» -a, • * « .\ 



IS J6 17 



IS 20 21 22 



?3 24- 25 26 27 



Various forms of malarial parasites (Thayer and Hewetson) : Figs. 1 to 10 inclusive, 
tertian organisms; Figs. 11 to 17 inclusive, quartan organisms; Figs. IS to 27 inclusive, 
estivo-autumnal organisms. 

Fig. 1. — Young hyaline form; 2, hyaline form with beginning pigmentation; 3, pig- 
mented form; 4, full-grown pigmented form; 5, 6, 7, 8, segmenting forms; 9, extracellular 
pigmented form ; 10, flagellate form. 

Fig. 11. — Young hyaline form; 12, 13, pigmented forms; 14, fully developed pig- 
mented form; 15, 16, segmenting forms; 17, flagellate form. 

Figs. IS, 19, 20. — Ring-like and cross-like hyaline forms; 21, 22, pigmented forms; 
23, 24, segmenting forms; 25, 26, 27, crescents. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 375 

blood a new generation of merozoites when schizogony is becoming 
feeble. According to this view, the gametocytes represent resistive 
forms which are able to withstand unfavorable conditions developed 
in the course of an infection (antibody formation?). The female, or 
macrogametocyte, is particularly resistive, may remain in the blood 
after other forms have disappeared, and may then by a process of 
parthenogenetic segmentation produce a new generation of merozoites. 
This theory would explain certain cases of late reappearance of infection 
after apparent recovery. 

Bass has lately succeeded in cultivating the asexual cycles in the 
species of vivax and falciparum by using equal parts of 0.5 per cent, 
glucose bouillon and blood, or Locke's fluid minus calcium chlorid plus 
ascitic fluid. The blood is defibrinated in flat-bottom tubes of such 
size that the clear fluid layer above the cells is at least \ inch in height. 
The parasites grow in the upper layer of red cells and can be transferred 
by a pipet to fresh tubes of uninjured cells for a secondary growth. 
Leukocytes and serum are prejudicial to the growth of the plasmodium; 
the former by phagocytosis, the latter by lytic effects. 

The Relations of the Mosquito to Malaria. — It has been positively 
demonstrated that when certain mosquitoes (of the genus Anopheles) 
are allowed to feed upon malarial patients and later upon normal indi- 
viduals, the latter acquire the disease. Also, it has been shown that 
susceptible persons may live in the most malarious districts without 
acquiring the disease, provided they are carefully screened from mos- 
quitoes. Some of the earlier investigations in this direction failed be- 
cause specimens of Culex and other genera (not Anopheles) were used. 
The Anopheles claviger, maculipennis, or quadrimaculata and others of 
this genus alone seem capable of conveying the disease. When the 
mosquito takes the blood of the malarial patient into its stomach 
(midintestine), flagellate forms (microgametocytes) are developed, and 
the flagella (microgametes) , each containing some part of the nuclear 
substance of the parent cell, are discharged, and, moving toward other 
of the parasites which do not form flagella (macrogametes) , fertilize 
these by penetration. The fertilized parasites then invade the intes- 
tinal walls, entering between the epithelia, and lodge in the surrounding 
tissues, where they segment and develop a distinct capsule. The cystic 
structures so formed (oocysts) contain numerous minute rods or sporo- 
zoites that have resulted from the segmentation of the parasite. The 
oocysts project into the ccelom cavity of the mosquito and eventually 
rupture into this, whence the sporozoites, discharged into it, are carried 
to different parts of the body and eventually to the salivary glands, from 
which they are introduced into any person subsequently stung by the 
insect. In this manner the extracorporeal cycle of development of the 
organism is completed and the perpetuation of the disease provided for. 

The recognition of the relation of the mosquito to malaria explains 
certain hitherto obscure facts regarding the conditions that favor the 
development of the disease. This knowledge has also led to the intro- 
duction of sanitary measures that have proved extremely useful. 



376 



A TEXT-BOOK OF PATHOLOGY 



Pathological Anatomy. — The most important fact in malarial 
infection is the destruction that it occasions in the blood. Rapid anemia 
with liberation of the hemoglobin (hemoglobinemia) and the appearance 
of granular pigment in the blood are among the results. The pigment 
accumulates in the spleen, liver, bone-marrow, and in other situations. 
Extreme disorganization of the blood may occasion hemoglobinuria and 
widespread pigmentation. Congestive enlargement of the spleen, and, 
after long-continued attacks, cirrhotic changes in that organ, may be 
observed. Thrombi of the capillaries and arterioles are not rare, and to 
these, in part at least, are due the focal necroses observed in the liver 
and elsewhere. The anemia is usually ascribed to the continued 
attacks of the parasites upon successive numbers of erythrocytes; 
some late observations lay the hemolysis to the circulation of free hema- 
tin, which substance, if injected into rabbits, produces a blood-picture 
like that seen in human malaria. 

Pathological Physiology. — The curiously paroxysmal seizures of 
malaria are probably the result of the liberation of toxic substances at 
the time of segmentation of the hematozoon. The periodicity depends 
upon the cycle of development of the organism. A single group 
of tertian organisms causes a tertian fever (a paroxysm every other 
day). Infection with two groups of tertian organisms, maturing 
on alternate days, produces a quotidian fever (a paroxysm every day). 
One group of quartan organisms causes quartan fever (a paroxysm 
every third day); three groups (maturing on successive days) cause 
quotidian fever. The febrile course in estivo-autumnal infection is 
more irregular, and this is explained by the discovery of organisms of 
various ages in the blood. Thus there results a constant succession of 
maturations and segmentations with less distinct periodicity, because 
the intervals which occur in tertian and quartan infection are wanting. 

Texas Fever of Cattle. — This disease is of interest in connection with 
malaria because of the relationship of the parasitic cause. The organism 
is a small, actively ameboid body which occupies the red blood-cor- 
puscles. Frequently it occurs in pairs in the corpuscles, and the name 
Pirosoma bigeminum was given to it on this account. Texas fever is 
characterized by acute fever and frequently by hemiglobinuria. The 
spleen is enlarged and hemorrhages are observed in various organs. 
When the blood of a diseased animal is injected into a healthy one, the 
latter acquires the disease. Transmission has been traced to the cattle 
tick (Ixodes bovis). The mother tick, after its detachment from the in- 
fected animal on which it has fed, transmits the infectious agent to its 
larvae through the ova. The young ticks then convey the infection to 
healthy cattle. 

Sporozoa in Birds and Cold-blooded Animals. — Many blood para- 
sites have been studied in birds, reptiles, and other cold-blooded ani- 
mals. In birds two species, Hcemojwoteus danalewskyi and Halteridium 
danalewskyi, have been closely studied, thus throwing much light on the 
life history of the malarial organisms. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



377 



COCCIDIA 
COCCIDIUM CUNICULI 

Description. — The coccidia are small bodies from 30 to 40 /i in 
length and from 15 to 20 p. in width, having a delicate outer coating, 
and within this a tough, double-contoured capsule. The body is filled 
with granular material, which is not rarely aggregated in the center. 
Outside the body sporulation takes place. The granular protoplasm 
divides into four rounded capsulated spores, each containing a granular 







Fig. 139. — Coccidium oviforme, showing method of reproduction. 

resting body lying in the concavity between two sickle-shaped daughter- 
spores. Sometimes endogenous sporulation is said to occur, the para- 
site simply breaking up into a large number of sickle-shaped bodies. 
The term psorospermicB is applied to the rounded spores found in the 
coccidium (Fig. 139). 




Fig. 140. — Coccidia in the wall of the bile-duct. The cut shows in the center active pro- 
liferation of the wall of the duct, with numerous ovoid coccidia massed in the tissue. 

The coccidium can also pass through a sexual reproduction (sporog- 
ony) with a cycle comparable to that of malarial parasites in the 
development of young and adult male and female forms. 

Occurrence and Pathogenesis. — The coccidium is a frequent para- 
site of rabbits and certain other animals. It leads to the formation of 



378 



A TEXT-BOOK OF PATHOLOGY 



yellowish nodules in the liver. It is an intracellular parasite, first in- 
vading the cells of the biliary passages and afterward the surrounding 
hepatic cells as well (Fig. 140). Less frequently it occurs in the intes- 
tinal tract, giving rise to nodular thickenings or ulcerations. 

The parasite escapes from the body in the stools and then under- 
goes sporulation. Other animals are probably infected by ingestion of 
the spores or sporulating coccidia. Occasionally the disease decimates 
rabbits or guinea-pigs kept in confinement. The animals become 
languid, lose their appetite, emaciate, and have fever. Later they 
suffer from convulsions, stupor or coma, and die in this condition. 

A few cases of coccidial disease of the liver have been observed in 
man. The lesions present themselves as cystic nodules springing from 
the bile-ducts, or less commonly as a diffuse involvement of the liver 
with cirrhosis and causing jaundice. Coccidial lesions of the intestines 
have also been discovered in man, and less commonly invasion of the 
heart, of the kidneys, and other parts. 

The close association of the organism with the lesions, and the 
number of organisms discovered in the tissues, justify the belief that 
it is the specific cause of the lesions. 

The coccidium of the intestinal tract is generally smaller and the 
sporulation more rapid than that of the hepatic form. It was, therefore, 
supposed by Leuckart to be a special variety, and has been called 
Coccidium perforans or C. hominis. More recently this has been re- 
garded as identical with the ordinary form. 

Coccidium Bigeminum (Stiles). — This variety has been found in dogs, 
cats, pole-cats, and man. The cyst divides into two parts and then forms 
four spores. 

Eimeria Hominis. — Eimeria is characterized by the formation in 
each adult parasite of a single spore containing an indefinite number of 
sporozoites. The Eimeria hominis was discovered in the purulent exu- 
date of a case of pleurisy. The spores were of large size and contained 
from ten to twenty sporozoites, accompanied by a protoplasmic rem- 
nant. The exact origin of the organisms in this case was not determined. 
Somewhat similar organisms were found by Virchow in a tumor of the 
liver, and by Severi in the lung. 

SARCOSPORIDIA 

The sarcosporidia, also called "Rainey's" and "Miescher's tubes," 
are met with in a number of mammals. The organism is composed of a 
protoplasmic mass covered with a capsule, and forming at the stage of 
maturity a large number of sickle-shaped or falciform sporozoites. 
The organisms usually occur in muscles, either within or between the 
muscle bundles, and are, therefore, elongated or tubular in shape. In 
connective tissues the organism may be rounded and sometimes grows 
to the size of a small cherry. Several varieties have been described, and 
a few observations have been made in man. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 379 



Infusoria 

BALANTIDIUM COLI 

Balantidium or Paramecium coli is a rounded body from 0.07 to 
0.1 mm. in length and slightly less in breadth (Fig. 141). It is sur- 
rounded by a coat of cilia closely set. There is an oral aperture at one 
end and an anal opening at the other. The substance of the parasite is 
granular, and contains a bean-shaped nucleus, within which is a round 
nucleolus and two contractile vacuoles, besides various foreign matters. 
The parasite possesses ameboid motion. Encysted forms with a thick- 
ened capsule have been described. 

Significance. — The hog is the natural host of this 
parasite. Man is probably infected through drink- 
ing-water or contaminated food-stuffs. It is found 
particularly in the northern countries of Europe, and 
occurs in cases of diarrhea, principally involving the 
large intestine. The parasite penetrates between the 
epithelial cells by its ameboid motion. Chronic catar- 
rhal inflammation and dysenteric lesions have been 
described. The lesions are chiefly purulent, necrotic, 
and ulcerative in the colon. The parasite may be antidium 1 ' ^oli 
found mixed with the degenerative mass. Occa- (Maimsten). 
sionally liver 'abscess is seen and a penetration to 
the blood-vessels has been observed. It is possible for it to penetrate 
the lymph-nodes of the intestinal wall or as far as the mesenteric glands. 
The organism is probably irritating, but whether pathogenic or not is 
unknown. Epidemics have been observed in monkeys, the manifesta- 
tion being prolonged diarrhea. 

Balantidium Minvtum. — This species resembles the Balantidium coli, but is 
smaller (40 « long), has a more prominent mouth, and but one vacuole. It has been 
found in association with Strongyloides, Ankylostoma, and Amoeba. Its significance 
is uncertain. 

ANIMAL PARASITES AND MOLLUSCUM CONTAGIOSUM 

Definition. — Molluscum or epithelioma contagiosum is an infectious 
disease of the skin marked by the appearance of white and pink papules. 

Etiology. — The cause of this disease is, no doubt, a micro-organism 
of some sort. Its contagiousness is evidenced by the occurrence of epi- 
demics in houses or asylums, by the occurrence of accidental inocula- 
tions, and by direct experiments. The incubation period seems to be a 
long one — sometimes extending to several months. The lesions have 
been found to contain small bodies whose resemblance to coccidia was 
long ago pointed out by Virchow. It is uncertain whether these are 
really parasites or epithelial degenerations. Some authors are positive 
regarding the parasitic nature of the bodies; others are equally con- 
vinced of their non-parasitic character. The most ably defended theory 




380 



A TEXT-BOOK OF PATHOLOGY 



for the parasitic nature of the virus ascribes it to an organism called 
Strongyloplasma hominis. 

It has been shown that the virus is filterable, and many consider 
it should be placed among the Chlamydozoa, The large pale body, 
with the later appearance of internal structure, seen only by appropriate 
staining, strongly supports this view. 

Appearances. — The disease occurs as single or, more frequently, 
multiple papules, at first quite small, but later becoming nodules of con- 
siderable size. In the larger a central depression or umbilication is seen, 
and on pressure cheesy matter may be expressed from this. After reach- 
ing about 3 or 4 mm. in diameter the papules remain stationary, or 
undergo softening and suppuration. In exceptional cases the tumor 
may reach the size of a small orange. 

Seats. — This disease occurs on the face, neck, chest, genitals, or 
sometimes scattered over the whole body, sparing only the palms and 
soles. The lesions have occasionally been found on the mucous mem- 
branes. 

Structure. — Microscopically, the lesions of this disease are found to 
consist of epithelial proliferations having a somewhat acinous arrange- 
ment, a hair-follicle occupying the center of each group of cells. The 
interior of the nodules is filled with soft, cheesy matter which may be 
expressed. The epithelial cells are arranged in several layers, the upper 
being normal cells with large nuclei, the deeper layers showing besides 
the nucleus, small droplets, or rounded spherules, the so-called molluscum 
bodies. These bodies grow in size and may be so large as to fill the cell, 
pushing the protoplasm and nucleus to one side. In this process the 
cell wall and protoplasm become horny, and practically the entire body 
consists of the enlarged molluscum corpuscle. Certain granulations 
and more or less definite segmentations within these bodies have been 
described as sporulating conditions. (See Skin.) 

Vermes 

Trematodes, or Fluke-worms 

The fluke-worms are usually flattened organisms, somewhat tongue 
shaped, and provided with powerful suckers and occasionally with 
hooklets. The intestinal canal begins in the oral orifice anteriorly, but 
is closed at the posterior extremity. Reproduction may take place 
directly or by the formation of an intermediate organism which . is 
parasitic to certain lower animals. In this stage they are actively motile, 
swimming about in water, and are known as the cercarise. Their action 
is irritative and obstructive. 

FASCIOLA HEPATICA OR DISTOMUM HEPATICUM 

The Fasciola hepatica, or liver-fluke, is from 15 to 35 mm. in length 
and 6 to 20 mm. in breadth; it is pointed at either end, and anteriorly 
is provided with two suckers, one at the head and one upon the ventral 
surface, somewhat posterior to the first (Fig. 142). The genital pore lies 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



381 



between the two suckers. The eggs are oval in shape, 0.14 to 0.15 mm. 
in length, and provided with a lid at one pole. 

The adult organism occupies the biliary ducts and is a frequent 
parasite of sheep. It is occasionally met with in man, usually occurring 

in considerable numbers. It gives 




Fig. 142. — The common liver-fluke (Fas- Fig. 143. — Ventral vein of a compressed 

ciola hepatica), enlarged to show the ana- specimen of a lung-fluke (P. westermanii) 
tomical characters (after Stiles). from a hog; greatly enlarged (after Stiles 

and Hassall). 

of the liver. The gall-ducts above the point of obstruction have 
sometimes been found considerably dilated or cystic. Clinically, ascites 
and jaundice have been found, with gastro-intestinal symptoms and 
fasciola eggs in the stools. 

DICROCffiLIUM LANCEATUM 

This form measures from 8 to 10 mm. in length and 2 to 2.5 mm. 
in breadth. The two suckers are far apart, and the genital pore lies 
between them. The eggs are 0.04 to 0.05 mm. in length and 0.03 mm. 
in breadth. 

This parasite is frequently associated with the previous one, and 
occupies the biliary passages of sheep and cattle. It is occasionally 
met with in other animals and in man. 



382 



A TEXT-BOOK OF PATHOLOGY 



OPISTHORCHIS FELINEUS 



This form varies in size with the degree of contraction, but is usually 
8 to 11 mm. in length and 1.5 to 2 mm. in breadth. The two suckers are 
far apart, and the genital pore is just in front of the ventral sucker. The 
eggs are oval, operculated, measuring 0.03 mm. in length and 0.01 mm. 
in breadth, and contain a ciliated embryo when deposited. This parasite 
inhabits the gall-bladder and bile-ducts of the domestic cat in particular, 
but is also found in the dog, fox, and man. It has been observed in 
France, Germany, Russia, Holland, Italy, and Japan. 



This parasite resembles the Opisthorchis felineus. The length is 
10 to 14 mm.; the breadth, 2.4 to 3.9 mm. The eggs are oval with 
a sharply defined operculum at the pointed pole; they measure 0.030 
mm. in length and 0.017 mm. in breadth. This parasite inhabits the 
bile-ducts and gall-bladder of domestic dogs and cats as well as of 
human subjects. It is found frequently in Japan, also in China and 
India. 

SCHISTOSOMUM HAEMATOBIUM OR DISTOMUM HAEMATOBIUM 

This organism, sometimes called Bilharzia, occurs in sexually dis- 
tinct forms, the male and female, however, occurring together. The 
male is 12 to 14 mm. in length and 1 mm. thick, 



and the body back of the large ventral sucker is 
somewhat flattened and curved ventralward to 
form a groove, in which the female is attached 
(Fig. 144). The latter is 16 to 18 mm. long, and 
0.13 mm. thick. The eggs are 0.135 to 0.180 mm. 
long and 0.055 to 0.060 mm. broad, not opercu- 
lated, and having a spine at one end or at the 
side of one end. The adult parasite occupies 
the portal vein and the veins of the spleen, 
mesentery, and the plexuses of the bladder and 
rectum. The eggs of the organism may be 
found in any of the organs, notably in the liver, 
in the intestinal walls, and in the mucous mem- 
branes of the urinary passages. They probably 




OPISTHORCHIS SINENSIS 





Fig. 144. — Schistosomum hsematobium, with eggs (von 
Jaksch). 



Fig. 145. — Papillary thick- 
ening of the mucous mem- 
brane of the bladder, show- 
ing schistosomum eggs in 
situ (Mosler and Peiper). 



occupy the vascular system ordinarily, but cause rupture of the walls 
of the vessels and thus escape into the tissues. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 383 

The pathological changes caused by this parasite and included in 
the term "bilharziasis" are more strikingly seen in the ureters and blad- 
der in acute cases. Hyperemic spots or small hemorrhages may be seen 
in the mucous membrane, and the surface is covered with blood-stained 
mucus containing the eggs. In cases of longer standing roughness of the 
mucous membranes and usualy small ecchymotic elevations or out- 
growths, suggesting papillomata, are observed (Fig. 145). Section 
through these shows that they consist of proliferated cells with enlarged 
blood-vessels, from which the adult worm may be removed. The 
tissues surrounding the vessels may contain eggs in enormous numbers. 
The mucous membrane is frequently covered with a calcareous deposit 
composed of urate and oxalate of sodium, and the excrescences may be 
converted into calcified polyps. Among the final results may be cica- 
tricial strictures of the ureter, pyelitis, and distention of the pelvis of the 
kidney, with atrophy of the kidney substance. Similar pathological 
processes may be found in the rectum. When the portal vein is occupied 
the eggs of the Bilharzia may be abundant in the liver substance. 
Schistosomum haematobium is a parasite occurring with enormous fre- 
quency in northern Africa and neighboring countries. It is compara- 
tively rare in other parts of the world. 

SCHISTOSOMUM JAPONICUM 

Schistosomum japonicum, or S. cattoi, has recently been discovered 
in eastern Asia and Japan. This parasite inhabits the arterial side 
of the portal system. It is somewhat smaller than Schistosomum 
haematobium, and the male is distinguished by his non-tuberculated 
integument. The ovum has no spine, is regularly oval, perfectly 
smooth, and with a much thinner shell. It resembles closely the ovum 
of Ankylostoma duodenale. The ova are deposited in the mucosa and 
submucosa of the large and small intestine, especially the former. From 
here they escape with the feces. No more is known of the life-history 
from this point than is the case with the Schistosomum haematobium. 
It causes a peculiar kind of chronic enteritis and anemia, associated with 
enlargement of the spleen and liver, terminating in a fatal cachexia. 
Cats are susceptible to this parasite as well as man. 

PARAGONIMUS WESTERMANII 

This organism is from 8 to 10 mm. in length and from 5 to 6 mm. in 
breadth. The eggs are brownish, and from 0.08 to 0.1 mm. in length. 
The worm occurs in the lungs, occupying excavated spaces, usually 
near the periphery of the organ. These cavities contain reddish or 
quite hemorrhagic mucopurulent liquid and abundant eggs. The cavi- 
ties are in communication with the bronchi, and clinically the disease is 
marked by cough and hemorrhagic expectoration or even repeated 
hemoptysis. The parasites themselves are rarely coughed up. The small 
tumors or burrows have also been found in the scrotum, liver, and brain. 



384 



A TEXT-BOOK OF PATHOLOGY 



In the brain they may give rise to grave nervous symptoms, often 
simulating those of intracranial tumor. This parasite occurs very 
frequently in Japan, China, and Corea, and has been observed several 
times in this country. 

OTHER FLUKE-WORMS 

Among other forms of fluke-worms of less importance are Fasciolopsis 
buskii, met with a few times in the intestine; Cotylogonimus heterophyes, 
Agamodistomum ophthalmobium, found in the lens of the eye; Opis- 
torchis noverca, occurring in the liver; and the Monostomulum lentis, 
occurring in the eye. The Gastrodiscas hominis occurs in the intestinal 
tract. Two forms, the Hexathyridium venarum and H. pinguicola, are 
possibly forms of encapsulated Fasciola hepatica. Fasciolopsis rathouisi 
is a fluke found in the intestinal canal of Asiatics. 

Cestodes, or Tapeworms 

General Biology. — The life-history of the different forms of tape- 
worms is much the same. They have two states of existence, the larval, 
which is generally found in one species of animals (the intermediary 
host), and the adult, usually occurring in another species (the host). 
It is supposed that in the case of one or two tapeworms an inter- 
mediary host is unnecessary, but this is doubtful. The adult worm, or 
tapeworm (strobile), occupies the intestinal tract of man or the lower 
(vertebrate) animals. It consists of a head (scolex), by which the worm 
fastens itself to the mucous surface; and after the head, a neck of greater 
or less size and length, and a body consisting of separate links or pro- 
glottides. The latter represent complete organisms, containing a com- 
plicated genital apparatus, hermaphroditic in nature, which produces 
numerous eggs. The eggs are partly discharged from the segments in 
the intestinal tract through a genital pore, but especially escape into 
the outer world when the ripe segments are separated from the body 
of the worm, are discharged from the bowel, and subsequently rupture 
and scatter the contained ova (Fig. 146). The egg or ovum encloses an 
immature larval organism, which, when received into a suitable inter- 
mediary host, penetrates the walls of the stomach or intestine and 
finds its way to the muscles or organs, where it embeds itself and forms 
the well-known measles (Figs. 146 and 147). These are seen with 
the naked eye as small cyst-like bodies lying between the muscle-fibers. 
They contain a scolex or head, like that of the adult worm, inverted into 
a sac filled with clear, watery liquid. When the measles or cysticerci 
occur in hollow cavities, such as the ventricles of the brain, they may 
reach considerable size. They differ somewhat in different forms of 
tapeworm, as will be described in connection with the individual species. 
When flesh infested with larval tapeworms is eaten by man or some 
suitable animal, the cysts are dissolved and the scolex fastens itself 
upon the mucous membrane of the intestine. The body of the worm 
is then slowly or rapidly formed. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



385 



Man is the host of tapeworms of adult or of larval type, most fre- 
quently the former. In one case, the Tcenia echinococcus, only the 
larval worm occurs in the human body, in the form of hydatid cysts. 




1 2 3 

Fig. 146. — Segments of (1) Taenia saginata; (2) Bothriocephalus latus; and (3) Taenia 
solium, showing arrangement of uterus. 

Pathological Physiology. — Adult tapeworms may exist in the intes- 
tines of man without causing disturbances of any kind. Frequently, 
however, digestive disturbances and pain and various reflex manifes- 




Fig. 147. — Eggs of various worms found in the alimentary canal of man: a, Ascaris 
lumbricoides; b, c, Oxyuris vermicularis; d, Trichocephalus trichiurus; e, Ankylostomum 
duodenale; r, Fasciola hepatica; g, Dicrocoelium lanceatum; h, Taenia solium; i, Taenia 
saginata; k, Dibothriocephalus latus; X 400. 

tations arise. These may be caused by the action of the worm as a 
simple foreign body, or may result from poisonous agents generated by 
the worm in its normal life, or as a consequence of death and degenera- 
tion of the segments. When there are many worms (as in the case 

25 



386 



A TEXT-BOOK OF PATHOLOGY 



of Hymenolepis nana) the disturbances of digestion may be largely 
mechanical; under similar circumstances, or when a single worm be- 
comes coiled and forms a mass, intestinal obstruction may be occasioned. 
In the case of Dibothriocephalus lotus poisonous substances are un- 
doubtedly produced, and to these must be ascribed the severe forms of 
anemia caused by this worm. The toxic substance is produced by the 
worm and is within its body, but can be absorbed by the intestine. 
That such occurs is indicated by the precipitation reaction between 
blood of patients and extracts from the worm. The poison is a hemo- 
lytic lipoid body. Other tapeworms rarely occasion anemia, and never 
the pernicious type just referred to. 

TvENIA SOLIUM 

This form, sometimes called the pork tapeworm, occurs in the 
adult state in man as a worm 2 or 3 meters in length; and in the hog 
or rarely in man in its larval condition. The head is about the size 
of a pin-head and very dark. Anteriorly it has a rostellum armed 
with a double row of from twenty-two to thirty-two hooklets. At 
the sides of the head are four suckers (Fig. 148). Attached to the head 
is a neck of thread-like appearance, which terminates at once in the 
fairly developed segments of the anterior part of the body. The seg- 
ments at first are broad and short, but become 
longer in proportion to the breadth toward the 
posterior end. The sexually mature segments 
are found at the middle and the posterior end 
of the worm. They contain a uterus consist- 
ing of a median tube and six to twelve lateral 
branches (see Fig. 146, 3). The genital pore is 
found at one side of the segment, irregularly 
alternating in successive proglottides. The 
eggs, which may be squeezed from the segments 
or obtained free in the feces, are either oval or 
spherical, from 0.030 to 0.035 mm. in diameter, 
and consist of a peripheral striated zone and a 
central granular portion, showing indistinctly 
Tseni'a "solium' (Mosler and six lines representing hooklets (see Fig. 146). 
Peiper )- Groups of segments may be discharged from 

the bowel from time to t ime, but this is not 
frequent; the discharge of single segments is quite unusual. The pro- 
glottides have independent movement, and may sometimes be seen to 
move about upon the bed-clothes. 

The cysticercus stage which gives rise to the Taenia solium lives 
normally in the intramuscular connective tissue and organs of the 
domestic pig, but it is known to exist also in a few other mammals as 
well as in man. 

The Larval State in Man. — When the ova are taken into the stom- 
ach the shell is digested and the embryo with its six hooklets is set free. 




< 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 387 



This penetrates the wall of the stomach or intestine, and in some un- 
certain manner reaches the muscles or organs, where it effects a lodg- 
ment. The hooklets are discarded and a little cyst containing clear 
liquid is formed, and at one point may be found a bud-like projection 
into the sac. This develops a scolex or head, which eventually becomes 
identical with the head of the fully formed worm. The cyst may be 
surrounded by a wall of reactive connective tissue. The duration of 
this process of formation of the cysticercus varies somewhat (five to ten 
or twelve weeks). The size of the cysts in the muscles varies from 
minute points to that of a pea. In the ventricles of the brain the 
cysticerci may be as large as a small cherry. Occasionally compound 
or racemose cysticerci are met with. 

In some cases the adult worm and the larval form have been found in 
the same individual (man). This is explained by the assumption that 



the eggs have reached the stomach, where the larvae have been set at 
liberty to penetrate the wall of the stomach and thus reach the tissues 
of the body. 

Among the seats of special interest are the brain, the muscles, espec- 
ially the peripheral muscles, tongue and heart muscle, and the sub- 
cutaneous tissues. 

The Adult Worm in Man. — When measled meat (hog, occasionally 
that of deer, sheep, and other animals) is eaten in insufficiently cooked 
form by man the capsules of the cysticerci (Fig. 149) are dissolved, the 
scolex attaches itself to the mucous membrane of the small intestine, 
and the worm is developed. Usually there is but one worm; occasion- 
ally several occur in the same case. The worm may remain in the 
intestine for years, despite repeated efforts to dislodge it. In other 
cases it is spontaneously discharged. Reverse peristalsis may cause 
portions to be carried to the stomach, whence they may be discharged 
by vomiting. 

Geographical Distribution. — The Taenia solium is an exceedingly 
rare parasite in America. It seems to be more common in certain parts 
of Europe. 




Fig. 149. — Measled pork; two-thirds the natural size (Leuckart). 



388 



A TEXT-BOOK OF PATHOLOGY 



TAENIA SAGINATA 



This form, sometimes called the beef tapeworm, is the common 
tapeworm of man. It is larger than the preceding form, being from 
4 to 8 meters in length, though it may reach a length of 35 meters. 
The head is large (2 mm. broad), cuboidal, and provided with four 
suckers. There is an abortive rostellum, but no hooklets (Fig. 150). 
The neck is rather long and slender and the segments rapidly become 
broader than long, but in the posterior half of the worm, where the 
sexually mature proglottides are found, the segments are longer than 
broad. The uterus is formed like that of the Taenia solium, but the 
lateral branches are more numerous (twenty to thirty, and often di- 



Fig. 150. — Head of Taenia saginata (Mosler Fig. 151. — Cysticercus of Taenia saginata; 



chotomously branched; see Fig. 146, 1). The eggs are rather more oval 
and larger than those of Tcenia solium, but otherwise closely resemble 
the latter. 

The larval form, or cysticercus, occurs in the ox and sometimes 
in the giraffe. The measles are found in the muscles, liver, lungs, and 
occasionally in other organs (Fig. 151). 

The adult form occurs only in man, and occupies the small intes- 
tine. The presence of the worm does not seem to occasion any definite 
disease of the intestines, except in rare cases, when a number are found 
present in a coiled mass, or when one worm is similarly coiled. This 
may cause intestinal obstruction, and possibly in exceptional instances 
rupture of the bowel. 

The symptoms ascribed to tapeworms are some of them doubtless 
reflex; but it is noteworthy that they are often absent until the patient 
discovers segments in the stools. (Further reference to possible patho- 
logical results is made in the discussion of Dibothriocephalus latus.) 
It is an exceedingly common parasite in certain countries (Africa and 
the East), but is more or less commonly found in all parts of the world. 

There is probably no precipitin reaction in the blood, but a comple- 
ment-fixing body has been found. 




and Peiper). 



natural size (Leuckart). 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 389 



HYMENOLEPIS NANA 

This form, sometimes called the dwarf tapeworm, in its adult state 
is 1 to 1.5 cm. in length (may reach 2.5 cm.) (Figs. 152 and 153). It has 
a rounded head, with a rostellum that may be 
protruded or retracted and that bears a single 
circle of twenty-two to thirty hooklets. The 
mature segments of the posterior end of the 
worm have a yellow color. The genital pore is 
on the same side in all the segments. The eggs 
are oval in shape, whitish and transparent; they 
are from 0.036 to 0.056 mm. long and 0.032 to 
0.042 mm. broad. 

The intermediary host of this form is not 
certainly known, but is supposed to be some 
form of insect or snail. In the rat the larval 
form occurs in the intestinal walls at the base 
of the villi in the form of a cysticercoid, which 
discharges its contained embryo into the intes- 
tine, where it matures. The same sequence 
may occur in man. The adult parasite alone 

I 

Fig. 152. — Hymenolepis nana, about nat- Fig. 153. — Hymenolepis nana, much en- 
ural size (Mosler and Peiper). larged (Mosler and Peiper). 

occurs in man. The head attaches itself deeply in the mucous mem- 
brane of the bowel, and may cause considerable local disturbance. 
There are usually several or many worms associated; sometimes there 
may be several thousands. 

HYMENOLEPIS DIMINUTA 

This form (probably identical with Taenia flavopundata) is from 
20 to 60 cm. in length; the head is elongated and verges gradually 
into the neck. The suckers are small, but there is neither rostellum nor 
hooklets. The segments are marked by a yellowish spot which repre- 
sents the male genital organs. It seems to be commonest in children. 
The intermediate host is a species of small moth (Asopia farinalis) . It 
has also been found in several other small insects. 





390 



A TEXT-BOOK OF PATHOLOGY 



DIPYLIDIUM CANINUM 



This form is identical with the worm formerly known as Tcenia 
elliptica, and is a common parasite of dogs and cats. The length is from 
15 to 30 cm.; the head is provided with a rostellum 
bearing sixty hooklets ranged in four rows; the ros- 
tellum may be protruded or retracted. At the junc- 
tion of the segments there is a considerable contraction 
of the diameter of the worm, giving the body a mark- 
edly linked character (Fig. 154). The mature seg- 
ments have a reddish-brown color from the presence 
of the eggs. Each proglottis has a double sexual ap- 
paratus, with a genital pore at each side. The inter- 
mediary host is probably the louse of the dog and oc- 
casionally the flea. The adult worm usually occurs 
in numbers in the intestinal tract, and in some cases 
seems to produce inflammatory disturbances. 



DAVAINEA MADAGASCARTENSIS 

This form is from 25 to 30 cm. in length; the head 
is marked by four large suckers and a rostellum bear- 
ing about ninety hooklets. 



1 



Fig. 154.— Dipyl- 
idium caninum 
(Mosler and Peiper) . 



TvENIA ECHINOCOCCUS 



The Tcenia echinococcus or Echinococcus granulosus in its adult 
form occurs in the upper part of the intestine of the dog, less commonly 
of the wolf and jackal, the larval condition occurring in 
man and in some of the lower animals. The mature 
worm is about 2.5 or 5 mm. in length, and consists of 
four segments (Fig. 155). The head, which constitutes 
the first, is provided with four suckers and a rostellum 
bearing two to four dozen hooklets in a double row. 
The second segment is about the breadth of the head, 
but somewhat shorter. The third is considerably larger; 
and the fourth is the largest of all, constituting about 
one-half or two-thirds of the entire worm. The uterus 
consists of a median portion with a few lateral branches. 
The eggs are oval, from 0.030 to 0.036 mm. in diameter, 
and the shell is rather thinner than in the eggs of other 
tapeworms. 

These eggs, deposited in water, or on vegetables, or 
conveyed by tactile communication from the body of 
the dog, are received into the mouth of man, and several of the lower 
animals and a few birds. From the stomach or intestine the embryo, 
liberated by solution of the egg capsule, bores its way into the vascular 
system, by which it may be conveyed to any part of the body of its host. 




Fig. 155.— 
Taenia echinococ- 
cus, enlarged 
(Mosler and Pei- 
per). 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



391 



Echinococcus Cysts. — When the eggs reach the stomach or, more 
probably, the intestine of man the embryo is freed and penetrates the 
mucous membrane. From each egg a sinele scolex or several scolices 



.MX 




JBl v^j SM- 

V\i^ A' -v" 



Fig. 156. — Finer structure of wall of echinococcus cyst, showing scolices in delicate cysts 
(from a specimen in the collection of Dr. Allen J. Smith). 

may arise (Fig. 156). The scolex is carried by the blood or lymphatic 
stream to the liver or other organs, where it develops an echinococcus cyst 
(Fig. 157), of which there may be several varieties. The wall of the cyst 




Fig. 157. — Echinococcus cyst of the liver (from a specimen in the Museum of the Phila- 
delphia Hospital). 

is composed of two layers, an outer cuticular and an inner parenchym- 
atous, granulocellular layer. The whole is surrounded by an adven- 
titious capsule of fibrous tissue derived from the organ of the host. 



392 



A TEXT-BOOK OF PATHOLOGY 



Within the cyst is a clear, limpid, sometimes amber-colored fluid, having 
a specific gravity of from 1009 to 1015, of neutral or alkaline reaction, 
and containing no albumin or only traces, but a considerable quantity of 
chlorid of sodium, cholesterol, and lipase have been found. A carbo- 
hydrate is sometimes found in the fluid. Hooklets are usually present 
and are of considerable diagnostic value. Such a cyst may increase in 
size, but with no alteration in its general structure, thus forming an 
acephalocyst (Laennec). This form is found in some of the lower animals 
and in cattle, where it may attain the size of an apple or an orange. 

In other cases large numbers of small hollow "brood capsules" 
are formed within the internal space, in which the order of layers 
is just the reverse to what it is in the parent cyst, that is, they are lined 
inside by a thin cuticle and have the parenchymatous layer on their 
external surface. From the "brood capsules" the scolices or echino- 
coccus heads develop as external protrusions, at the distal end of which 
the suckers and hooklets of the scolex are formed (Fig. 158). Some 
claim that the scolices may develop directly from the cyst wall without 
the medium of the brood capsules. To this form is given the term 
Echinococcus veterinorwn or E. sco- ■ 
licipariens. It occurs chiefly in 
domesticated animals. 





Fig. 158. — Formation of "brood cap- 
sules" upon the parenchymatous layer 
(Leuckart) . 



Fig. 



159. — Echinococcus multilocularis 
(Luschka) . 



In man and only rarely in cattle the mother-cyst may develop 
"daughter-cysts," which, though smaller than the parent, resemble it in 
the structure of their walls, which are covered externally by a stratified 
cuticle and internally by the parenchymatous layer. They arise from 
small detached portions of the parenchymatous layer in the strata 
of the cuticle of the mother-cyst; they may bulge inwardly or outwardly 
and may separate themselves entirely from the mother-cyst. The 
"daughter-cysts" may remain sterile or may produce brood capsules 
and scolices or other cysts ("granddaughter-cysts"). To this cyst the 
term "hydatid," or Echinococcus hominis or E. altricipariens is applied. 

There is another form of echinococcus occurring in man as well as 
in animals and termed Echinococcus multilocularis (Fig. 159). It varies 
from the size of a fist to a child's head, presents a collection of cysts 
from 0.1 to 5 mm. in diameter, and is embedded in a connective-tissue 
stroma. Each cyst is covered with stratified cuticle, and according 
to the size contains either solid cellular contents or a cavity lined with 
a parenchymatous layer. The fluid in this cavity may be transparent 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 393 



or opaque, due to the presence of fat globules, bile-pigment if the cyst 
be in the liver, hematoidin, and fat crystals. The cysts are usually sterile, 
though scolices may be present in some. In man the center of the mass 
disintegrates, leaving a large cavity filled with a brown or greenish 
fluid containing shreds of the wall, calcareous bodies, small cysts, 
scolices and hooklets, fat, hematoidin, margarin, cholesterin, and con- 
cretions of lime. Nothing positive is known as to the development 
of this form, that is, whether it springs from a single oncosphere or 
from a number of oncospheres, or whether its conformation is brought 
about by peculiarities in its surroundings. 

Echinococcus cysts may continue to grow until they have reached 
huge dimensions without undergoing any secondary changes. In 
other cases the parasite may die and the growth may cease, or active 
proliferation of the tissues around the cyst may lead to early destruction. 
In still other cases suppurative change occurs in the cyst or its wall. 
In all cases when the cyst reaches a certain size the tissues around it 
produce a connective-tissue capsule of greater or less thickness. When 
the parasite dies, inspissation of the liquid occurs, and it may eventually 
disappear or be converted into a thick whitish material; the cyst walls 
and the connective-tissue capsule at the same time shrivel and present 
peculiar concentric lamellations that are very characteristic. Event- 
ually calcification of the wall of the cyst and, to a certain extent, of its 
contents takes place. 

The blood of patients suffering from hydatid disease will fix the 
complement away from the hemolytic series if the contents of a cyst be 
used as antigen. This complement-fixation may be used diagnostically. 
The contents of the cyst seem to be toxic, for if they escape in the body 
a severe intoxication results, taking the form of local irritation, inflam- 
mation, fever, and urticaria. 

Seats. — Echinococcus cysts are most frequent in the liver. They 
also occur in the lungs, kidneys, spleen, and omentum, and less frequently 
in the brain or other parts of the nervous system. The pathological effects 
are usually produced by direct mechanical pressure, but may be due to 
the toxin as noted above. 

The geographical distribution is extensive, but the disease is com- 
mon only in restricted localities, especially in northern countries (north 
of Europe, Iceland). 

DIBOTHRIO CEPHALUS LATUS 

The Dibothriocephalus lotus is the largest tapeworm of man, 
reaching the length of from 2 to 9 meters or more. The head is flat- 
tened and club shaped and presents two groove-like suckers at its 
sides (Fig. 160). The neck is thin and gradually increases in diameter. 
The ripe segments are quadrate, and are distinguished by a rosette-like 
formation of the uterus, which is plainly visible in the center of each 
proglottis (see Fig. 146, 2). The genital pore is upon the flat surface of 
the segment and always upon the same side of the worm. The eggs are 



394 



A TEXT-BOOK OF PATHOLOGY 



oval in shape and enclosed in a shell presenting a hinged lid at one pole. 
The intermediary host is some form of fish, most frequently the pike. 
The eggs first undergo a certain amount of development in water, the 
embryo becoming free and floating about, or being 
propelled by a ciliated outer covering, and then en- 
tering the digestive tract of fish. Transmission of 
the parasite to its human host is believed to be con- 
fined to the eating of the flesh of infected fish im- 
perfectly salted or cooked. 

The toxic effect of this worm is believed to be 
due to a hemolytic lipoid which is excreted by the 
worm or liberated by its enzymes when acting upon 
Fig. 160.— Head detached proglottides. Extracts of the worm have 
and neck of Diboth- a marked digestive power on protein. 

nocephalus latus m, , . « , ., , 

(Leuckart). The geographical distribution is comparatively 

restricted. It is frequent in certain northern coun- 
tries, as in Sweden and in parts of central Europe, especially in 
Switzerland. It is only occasionally met with in America in immi- 
grants. 

DIBOTHRIOCEPHALUS CORDATUS 

This variety is much smaller than the last, the maximum being 
from 1 to 1.25 ix. The head is short, broad, and heart shaped, and the 
suckers are placed upon the flat surface. The uterine structure differs 
from that of Dibothriocephalu.s latus in being narrower and more elon- 
gated, and also in having lateral branches. The body of the worm con- 
tains granular calcareous matter. This parasite is found commonly 
in the seal, the walrus, and the dog in Greenland and Iceland, occa- 
sionally in man also. No doubt its larva lives in fishes. 




BOTHRIO CEPHALUS MANSONI 

This variety occurs only in the larval form in man, nothing being 
known of the character of the adult worm. It has been found in the 
region of the loins, in the urinary passages, and in the tissues about 
the eyes. The head of the worm is distinguished by a papilla-like 
projection. 

DIPLOGONOPORUS GRANDIS 

This parasite measures up to 10 meters in length. The scolex is 
unknown. On the ventral surface are two grooves in which lie the 
genital pores. The ova are brownish, oval, measuring 0.063 mm. in 
length and 0.048 mm. in width. It has been observed in Japan. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 395 



Nematodes, or Round-worms 



ASCARIS LUMBRICOIDES 

The Ascaris lumbricoides , or ordinary round-worm, is one of the most 
frequent intestinal parasites. The male may reach a length of 25 cm. and 
a thickness of 2 to 4 mm. ; the female is longer, up to 40 cm., and thicker, 
up to 5 or 6 mm. The body of the worm is 
brownish or sometimes pinkish in color, and pre- 
sents parallel ridges or rings somewhat like those 
of the earth-worm. The head is provided with 
three rounded prominences or lips, between 
which the mouth is placed (Fig. 161). The male 
shows two chitinous spicules at the cloaca. The 
eggs of the worm are produced in great numbers ; 
they are elliptical, measuring 0.05 to 0.07 mm. 
in length, and 0.04 to 0.05 in breadth and are 
covered with a tough shell, surrounding which 
is a clear material in an irregular mass. The 
contents of the eggs consist of a granular ma- 
terial, sometimes showing the linear outlines of 
an embryo. 

The ascaris develops in man from swallow- 
ing the eggs in infested drinking-water or food. 
The parasites may be present singly or in num- 
bers. They occupy the small intestine, but fre- 
quently migrate, entering the gall-ducts, the 
stomach, the esophagus, and even the larynx 
or nasal cavities. 

Pathological Physiology. — Ascarides may 
give rise to violent symptoms by obstruction of 
various passage-ways, and when in numbers or 
united in masses even intestinal obstruction may 
be caused. It is probable that ascarides produce 
irritating secretions, as it has been observed 
that considerable dermatitis sometimes arises in 
persons handling them. The toxic action has 
been ascribed to fatty acids and irritating vola- 
tile aldehyds which have been found in them 
cavities containing lumbricoids are found in connection with ulcera- 
tions and perforation of the intestines. These abscesses were believed 
by older authors to be caused by the worms; at the present time it is 
more generally held that the worms play no important part, their 
presence being due only to their coincidence in the intestine. 




Fig. 161. — Ascaris lumbri- 
coides: A, female; B, male; 
C, egg, magnified 300 diam- 
eters; b, head, magnified 
(after Perls). 

Occasionallv abscess 



ASCARIS CANIS 



This form, which is common in cats and dogs, is rarely met with 
in man. It is much smaller than the ordinary round-worm, the male 



396 



A TEXT-BOOK OF PATHOLOGY 



reaching a length of 45 or 60 mm., and the female 120 to 130 mm. 
The head is distinguished by two lateral wing-like projections com- 
posed of chitinous material. 



OXYURIS VERMICULARIS 

The oxyuris, seat-worm, or pin-worm, is one of the commonest para- 
sites of man. The male is 2.5 to 5 mm. in length; the female, 10 to 12 
mm. (Fig. 162). The posterior end of the male is blunt and curved 
upon itself; in the female it is elongated. The eggs of the oxyuris, which 
are produced in great numbers, are oval or elliptical and about 0.05 mm. 
long. The embryo is visible within as a tabulated body. The parasite 
a h is developed directly from the eggs. When 

JMMBWHHBi these arc swallowed the outer coating is dis- 

solved in the stomach and the embryos escape, 
to reach their full development in the small in- 
testine. The impregnation occurs in the small 
_ ! intestine within a short time after the swallow- 

Fig. 162.— Oxyuris ver- ing of the eggs. After impregnation and ripen- 
micularis: a, female; b, m „ th e female parasites move toward the rectum 

male (Mosler and Peiper). i t i i i 1 1 • 

and may be discharged, or may leave by their 
own movements. The life of the worm is short, but there is always 
the possibility of reinfection. 

Oxyuris is especially common in childhood. It is probable that 
the worms sometimes cause inflammatory troubles. In cases in which 
they accumulate in numbers a form of verminous diarrhea may be pro- 
duced. 

In female children vaginitis frequently results from the migration 
of the parasites into the vagina. 



TRICHINELLA SPIRALIS 

This organism occurs in its larval form in the muscles or organs of 
man and in the lower animals; in the adult form it is found in the intes- 
tines of man or animals. 

The adult male is about 1.5 mm. in length and 0.04 mm. in thick- 
ness. At the posterior end there is a retractile cloaca flanked by two 
projections. The female is 2 to 4 mm. in length and 0.06 mm. in thick- 
ness. The eggs are provided with a very thin shell, and the embryos 
escape from this within the uterus. They are produced in immense 
numbers. The young embryos found in the intestinal tract are from 
0.1 to 0.16 mm. in length, the anterior end being thicker than the pos- 
terior. 

In part they escape with the feces and die; the greater part pene- 
trate the intestinal wall and are carried to various parts of the system, 
embedding themselves especially in the muscles, where they undergo 
further changes. Here the organism coils itself and becomes 
surrounded with a capsule, which is at first transparent, but 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 397 

may subsequently undergo calcareous change and become opaque 
(Fig. 163). 

Trichinellse are acquired by man by eating improperly cooked ham. 
The capsules are digested and the larval trichinellae set free. In the small 
intestine they reach their maturity in about three days; here impregna- 
tion takes place, after which the males die, while the females either 
bore more or less deeply into the villi or, by way of the glands of Lieber- 
kiihn, penetrate the mucous membrane, and 
so reach the lymphatic spaces, where they 
deposit their young. These are disseminated 
throughout the body by their own migra- 
tions or by means of the lymph- and blood- 
streams. 

The favorite seat is the striated muscle 
tissue, and they lie within the muscle bun- 
dles themselves or, less frequently, between 
them. They reach their destination in ten 
days after the primary invasion, but subse- 
quent crops are deposited as the young con- 
tinue to mature in the intestines. In two 
or three weeks they begin to become encysted in the muscles, where 
they remain alive, capable of development for many years. 

When the embryos are liberated in the stomach and intestines they 
occasion violent gastro-intestinal irritation, with vomiting, diarrhea, 
and often more or less pronounced collapse. In their later migration 
the worms set up intense muscular pains of rheumatoid character, with 
edematous swelling and fever. The disseminated disease is called 
"trichiniasis." The pathology of this condition includes, besides myo- 
sitis and gastro-enteritis, fatty liver, nephritis, and infarcts. There is 
undoubtedly an irritative toxin produced, but whether this is wholly 
within the worm or in part made from the degeneration of muscle 
tissue is not certain. There is usually a marked eosinophile increase, 
the cells arising in the bone-marrow from toxin action. The worm uses 
the glycogen stored in the muscles during its growth. No passive im- 
munity can be produced with the blood of injected animals. 

Trichiniasis is common in all parts of the world, but has been largely 
reduced by greater care in the cooking of pork. 

ANKYLOSTOMA DUODENALE OR UNCINARIA 
DUODENALIS 

The Ankylostoma duodenale is a cylindrical worm, the female 
being from 12 to 18 mm. in length; the male, from 8 to 10 mm. 
The head is rounded, bent back like a hook, and is armed with 
six sharp, hook-like teeth, two pairs ventrally, one pair dorsally. 
The female is usually of a brownish or reddish color, due to the ab- 
sorption of coloring-matter from the blood. The elliptical eggs are 
easily distinguished, from 0.056 to 0.063 mm. in length and 0.036 to 0.04 




a b 



Fig. 163. — Trichinella cap- 
sule with its connective-tissue 
covering: a, early stage; b, 
calcified (Leuckart). 



398 



A TEXT-BOOK OF PATHOLOGY 



mm. in thickness. The shell is separated from the contents, and the 
latter have a granular appearance, are brownish, and in a state of seg- 
mentation. The eggs may appear in the stools in great numbers. If 
now they meet with the proper conditions, chief of which are a warm 
climate and damp earth, they hatch out and the active embryo is set 
free. It rapidly acquires organs of digestion and, after casting its skin 
several times and undergoing other evolutionary changes, is ready to 
re-enter a human host. Loos has proved quite conclusively that, while 
the organism may rarely enter the human alimentary canal by the mouth, 
the probable method of entrance is far more complicated. 

After completing its exogenous phase of development, a suitable 
opportunity offering, the little worm penetrates the skin, generally of the 
feet and legs, of the coolies or others working in or passing through the 
contaminated earth in which the ankylostome ova had been previously 
deposited. The embryo enters the skin through some follicle, thence 




Fig. 164. — Ankylostoma duodenale: a, Male, natural size; b, female, natural size; c, male, 
magnified; d, female, magnified; e, head, greatly magnified; /, /, /, eggs (von Jaksch). 

passes into a blood-vessel, and so is carried finally to the lungs. Here 
it leaves the blood-vessels and, undergoing further changes to enable it 
to resist the gastric juice, enters an air vesicle, passes to a bronchus, and 
so, by way of the trachea, esophagus, and stomach, finally arriving at 
the small intestine. Sexual characters are now assumed and reproduc- 
tion commences, the ova falling into the contents of the gut and so passed 
out in the stools. 

The adult worm may be present in small or large numbers, and is 
usually rather firmly attached to the mucous membrane. Changes in 
the latter, however, are not pronounced. 

The method of entrance of the ankylostome to its human host 
throws important light on the condition known as "coolie itch" or 
"ground itch," which often is a forerunner of the intense anemia and 
other symptoms of the condition known as ankylostomiasis; "coolie 
itch" is a sort of papulopustular dermatitis generally attacking the 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 399 



feet and legs, and at times other surfaces as well, of the coolie laborers on 
plantations. It is probably caused by the passage of the ankylostome 
embryos through the skin. Ankylostomiasis or uncinariasis is charac- 
terized by severe and intense anemia, abdominal discomfort or pain, 
general wasting, often followed by death. This parasite was also found 
in many cases of Egyptian chlorosis, and was the cause of the intense 
anemias (pernicious anemia) of the laborers engaged in building the 
St. Gotthard tunnel. 



NECATOR AMERICANUS OR UNCINARIA AMERICANA 

This parasite is shorter and more slender than the Ankylostoma 
duodenale, the male being 6 to 9 mm. long, and the female 8 to 15 mm. 





Fig. 165. — A, Dorsal view of head end of Ankylostoma duodenale; B, dorsal view of head 
end of Necator americanus. (Drawn to scale to show difference in size. A. J. Smith.) 



long. There are also minute differences in the head and body, though 
the general structure of the two parasites is the same. In place of the 




Fig. 166. — A, Caudal bursa and tail of male Ankylostoma duodenale; B, caudal bursa 
and tail of male Necator americanus. (Drawn to scale to show difference in size. A. J. 
Smith.) 

ventral and dorsal oval teeth there are plates or suckers, while deep in 
the mouth opening there is one central tooth and one pair of narrow 




Fig. 167. — Ova of (A) Ankylostoma duodenale; (B) Necator americanus. (Drawn to 
scale to show comparative size. A. J. Smith.) 

straight teeth ventrally and dorsally. The ova are larger than those of 
the Ankylostoma duodenale, being 0.068 mm. in length and 0.038 mm. 



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A TEXT-BOOK OF PATHOLOGY 



in breadth, otherwise they are similar. This form has been found 
especially in tropical and subtropical America and in the West Indian 
islands. The conditions produced by the American hookworm are 
similar to those caused by the Old World form, but are probably less 
intense. 

The pathological effect of uncinariasis is toxic. The worms remove 
some blood from the gut wall for their nourishment, but not enough to 
cause the severe anemia of the disease. Small hemorrhages appear in 
the gut. A weak hemolysin is formed, can be extracted from the worm, 
and is probably absorbed by the intestine. There is also an active 
coagulating body in the head of the dog hookworm. There are to be 
found in the body fatty degeneration and hyperplasia of the bone- 
marrow. 

STRONGYLOSES INTESTINALIS 

This parasite occurs in two generations or types: the parasitic, 
in which the individual of female habitus represents both sexes and 
reproduces by parthenogenesis; and the free living generation, in which 
the two sexes are represented by different individuals. The parasitic 
generation {Anguillula intestinalis) lives in the upper intestinal tract, 
boring deeply into the mucous membrane and frequently into the epi- 
thelium of Lieberkuhn's glands both for nourishment and oviposition. 
This form is 2.2 mm. in length and 0.034 mm. in breadth; the mouth is 
surrounded by four lips, the esophagus is almost cylindrical and a quar- 
ter the length of the entire body; the eggs measure 0.050 to 0.058 mm. 
in length and 0.030 to 0.034 mm. in breadth. The eggs develop in the 
intestinal wall, and the rhabditiform larvae, which measure 0.2 mm. in 
length, reach the lumen of the intestine and grow to double or three 
times that size until they are passed out with the feces. With the 
proper temperature (26° to 35° C.; 78.8°-95° F.) they develop in about 
thirty hours into the free living generation (Anguillula stercoralis). 
This form is sexually differentiated; its body is smooth and cylindrical, 
with pointed tail end. The mouth has four distinct lips; the esophagus 
is short with a double (rhabditic-like) dilatation; there are three small 
curved spicules at the base of the tail. In the males the posterior end is 
rolled up, in the females it is straight and pointed. The males measure 
0.7 mm. in length and 0.035 mm. in breadth. The females measure 1 mm. 
in length and 0.05 mm. in breadth. The ova are thin shelled, yellowish, 
and measure 0.07 mm. in length and 0.045 mm. in breadth. The embryo 
as it emerges from the egg often within the uterus measures 0.22 mm. 
in length and resembles the parent form. After growing to about 0.55 
mm. in length it moults and then takes on the characteristics of the 
parasitic form (strongyloid or filariform larvae). In the European 
strongyloides the free living generation is absent. This may also be 
true in the strongyloides of tropical origin where external conditions 
are unfavorable to the development of the rhabditic form. 

There are, as has been mentioned, two methods of reproduction: 
that by direct transformation of the rhabditiform larvae into filariform 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 401 



and then into adults, and the indirect, through the intermediate genera- 
tion. By this arrangement the parasite may reproduce directly if 
external conditions are unfavorable, and indirectly when conditions are 
favorable. The latter method seems to be more common in the tropics 
than in colder countries. The adult form alone is parasitic in the true 
sense; the other form representing only a stage for the perpetuation 
of the species. Unlike the ankylostome, eggs of strongyloides are 
rarely found in the stools excepting after purgation. Infection prob- 
ably occurs through tainted water and food, but some experiments seem 
to indicate that the embryo may penetrate through the skin and thus 
gain access to the body. 

Strongyloides is common in tropical countries, and was first dis- 
covered in cases of Cochin China diarrhea. It is probably capable of 
causing intestinal irritation, and seems rarely present in healthy persons, 
but its pathogenicity is still uncertain. It has recently been discov- 
ered in the United States. 

TRICHOCEPHALUS TRICHIURUS 

The anterior portion of this parasite is thin and thread-like, while 
the posterior portion is thicker. The length of the worm is from 4 to 
5 cm., the male being somewhat the smaller. The thicker part of the 
male is curled upon itself and blunt at 
the end, while that of the female is 
straight and more pointed (Fig. 168). 
The eggs are very characteristic, being 
brownish in color, covered with a thick 
capsule, and having at either pole a 
button-like projection (see Fig. 146, d). Fig 168 ._ Tr i c hocephaius trichi- 

The egg is 0.050 to 0.054 mm. in length urus; natural size: a, Female; b, male 

and 0.023 mm. in breadth. (HeUer) - 

The parasite, commonly known as the "whip-worm," occupies the 
cecum in man, occasionally the vermiform appendix, and sometimes 
the small intestine. It is one of the most common intestinal parasites 
in this country and appears to be well distributed over the entire surface 
of the globe, being particularly frequent in children in Syria and Egypt. 
It does not, as a rule, produce serious disturbance, but may cause in- 
testinal or reflex nervous symptoms. Recently it has been claimed that 
the parasite causes considerable disturbance by abstracting blood and 
producing a soluble toxin. 

FILARIA MEDINENSIS 

The Filaria or Dracunculus medinensis is a round-worm infesting 
the subcutaneous tissue and the skin. The male has not been recog- 
nized with certainty, though two observers have found a smaller 
degenerated and partly calcified form in association with the female 
filaria. The female sometimes reaches a length of 50 to 80 cm.; it is 

26 




402 



A TEXT-BOOK OF PATHOLOGY 



yellowish in color and exceedingly elastic; the anterior extremity is 
roundish, the posterior terminating in a spine. In general appearance 
it resembles a string of catgut. The body of the worm contains a highly 
developed uterus, which practically fills the cavity of the worm, the 
intestinal tube being crowded to one side. The uterus is found to con- 
tain innumerable small embryos; these escape when the parasite is rup- 
tured. 

The process or place of impregnation is unknown. When ovulation, 
however, is completed the parasite moves down to the leg or foot of her 
host, whence she will be better able to deposit her young in water, which 
is absolutely necessary for their development. Here she drills a small 
hole in the derma, but does not penetrate the epidermis. Over this a 
small blister or bulla forms which soon ruptures, disclosing the small 
opening in the center of a superficial erosion. When the host now enters 
the water a portion of the uterine tube is forced out through the mouth 
of the worm by the contraction of the musculocutaneous integument 
and ruptures, setting free myriads of the embryo worms. This is re- 
peated at intervals until the entire uterus is expelled and parturition 
is completed. This takes, as a rule, two to three weeks. The worm now 
dies, and is expelled or pulled out bit by bit or entire, with or without 
suppuration. Forcible attempts at removal of the worm from the tis- 
sues may result in its rupture, thus setting free millions of embryos in the 
tissues, whose presence, associated with suppuration, which usually 
follows, results in a condition of considerable danger to the patient. 
It is, therefore, better to wait until parturition is completed before 
attempting removal of the worm. 

The embryos having been deposited in the water take up their abode 
in the intermediary host, the body cavities of a species of cyclops. They 
enter by penetrating the delicate membrane that unites the plates of the 
ectoskeleton of the crustacean. The life-history from here on is a blank. 
It has been thought that after proper development the parasite is swal- 
lowed in drinking-water while still in the body of the crustacean, or it 
may be after it has escaped from this intermediary. Or it may obtain 
entrance to its human host by boring its way through the skin. 

The organism occurs very abundantly in tropical countries of the Old 
World, notably Arabia, along the coast of the Caspian Sea, in Abyssinia, 
and Guinea. The parasite is sometimes called the Guinea-worm. 

FILARIA BANCROFTI 

Several varieties of filariae have been found in the blood and are 
included under this generic term. The discovery of the organism 
or, rather, of the embryos was made by Wucherer in a case of hema- 
turia. 

The embryos of Filaria bancrofti or F. sanguinis hominis appear in 
the blood, urine, the lymph, and the tissues as thread-like structures, 
varying in size in the different varieties. The ordinary form has a 
thickness of about the diameter of a red corpuscle, and is as much as 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 403 



0.13 to 0.3 mm. in length. It consists of a transparent sheath, almost 
completely filled with the embryo, the ends, however, projecting a little 
beyond the organism in a sac-like fashion (Fig. 169). The embryo is 
actively motile, squirming, thrashing, or curling and uncurling itself 
rapidly, and thus producing more or less agitation of the corpuscles or 
solid bodies in its vicinity. 

The number of the embryos found in the blood varies greatly; in 
many cases a search through several cover-glass preparations may be 
necessary to detect a single one. Usually they are more abundant. 
A feature of importance is that they occur only during the night, 
unless the patient reverses the usual conditions and rests during the 
day. 

The adult worms occupy the lymphatic channels, the male and female 
being found together. The male is colorless and measures about 40 mm. 
in length and 0.1 mm. in thickness. The cephalic extremity is a little 
thickened, the posterior extremity is bent and rounded, but not spiral. 
The female is brownish, 76 to 80 mm. in length and 0.2 to 0.3 mm. in 
thickness. Both extremities are rounded. Almost the entire body 




.mm: 

Wo CP 3 



G 



Fig. 169. — Filaria embryo, alive in the blood (F. P. Henry). 



is occupied by the two uterine tubes, in which may be seen the ova and 
already developed larval filarise. These enter the circulation and are 
discharged in various ways, especially in the urine. The common 
tropical mosquito (Culex fatigans) has been found to act as the inter- 
mediary host in which the embryo reaches its fuller development. The 
embryo filaria? are taken into the midgut of the mosquito together with a 
certain amount of blood at a time when the filarise are found in the 
peripheral circulation. Here in the thickened plasma the embryos 
are able by their active movements to break through their sheath. 
Now, by means of a short delicate spine and a circle of hooked lips at 
the head end, the organism bores its way to the thoracic muscles of the 
mosquito. Here in the course of one to three weeks it goes through a 
series of changes and increases considerably in size. It now works its 
way to the head of the mosquito, and finally passes down into the 
labium or sheath of the proboscis, where it awaits the opportunity to 
enter a human host when the mosquito next feeds on man. It then finds 
its way into the lymphatic trunks, where the sexes come together and the 
young are born. 



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Filariasis is particularly common in the warmer climates, but is 
occasionally met with in this country, especially in the Southern States. 
One of its most frequent forms is characterized clinically by hemato- 
chyluria. The embryos in these cases may be found in the blood and also 
in the chylous urine. Pathologically, no gross changes may be found, 
but there may be in other cases evident distention of the lymphatic 
channels and blood-vessels of the pelvis of the kidneys, ureters, or 
bladder; and the embryos may be found in the substance of the kidneys 
or in the walls of the blood-vessels. Another form of filariasis is ele- 
phantiasis. In these cases there is obstruction of the lymphatic vessels 
in consequence of the presence of the parasites, of thrombi, or of inflam- 
matory lesions, and as a result of these conditions dilatation of the 
peripheral lymphatic vessels occurs. The skin may be ruptured and 
chylous liquid may exude. The embryos may be found in this on micro- 
scopical examination. 

Varieties. — Manson has described three varieties of embryonal 
filarise — the original form, or Filaria nocturna; a second variety, in 
which the embryos are found at any time, night or day, called Filaria 
perstans, characterized also by its small size (0.2 mm. in length), great 
motility, and absence of a sheath; this he believes is the cause of certain 
skin diseases (craw-craw) of Africa; the adult worm is unknown. The 
third form is the Filaria diurna, which appears in the blood only during 
the day. The last is probably the embryo of Filaria loa, a wandering 
form frequently occurring in the eye, lying under the conjunctiva. It 
is found in Africa and tropical America. Manson believes that the 
mangrove fly is the intermediary host. 

OTHER FORMS OF FILARDE 

The Filaria lentis was found in the lens in a case of cataract; the 
F. labialis was discovered in a pustule on the lip of a student in 
Naples; the F. hominis oris was found by Leidy in the mouth of a 
child; and F. restiformis was found in the urine of a patient by the 
same observer. The F. immitis is the common filaria of the dog, and 
has been found in man. The F. ozzardi was found in the blood of 
Caribs of British Guiana. The F. loa is confined to Western Africa. 
The F. bronchialis was found in the bronchial lymphatic glands in a 
case of phthisis, and has also been found in the trachea and bronchi. 
The F. demarquayi and F. magalhcesi are forms whose identity has not 
been sufficiently established. F. conjunctiva?, F. lymphatica, and F. 
romanorum-orientalis are others that have been described. 

ECHINORHYNCHUS GIGAS 

This is a large round-worm, the body being marked by distinct, 
transverse, parallel rings. The male may be from 7 to 10 cm. in length, 
the female from 31 to 50 cm. There is a retractile rostellum, with six 
rows of hooklets at the anterior end, each row composed of eight spicules. 
The parasite occupies the small intestine of the hog, and has been found 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 405 



occasionally in man. The intermediate host seems to be the grub of the 
cockchafer and the June-bug. 

Other varieties of echinorhynchus have been described, but are not 
well-determined species. 

EUSTRONGYLUS GIGAS 

The female of this species may reach a length of 1 meter; the male is 
but one-third the size. The anterior end of the worm is retracted and 
the mouth surrounded by six papillae. The posterior end is expanded 
and provided with a spicule projecting from the cloaca. The color of the 
worm is brownish or blood red. The parasite is found in the pelvis of the 
kidneys, ureters, and bladder of dogs, horses, cattle and other animals, 
and rarely in man. Among its results are enlargement of the pelvis of the 
kidney and atrophy of the kidney substance. 

STRONGYLUS APRI 

This parasite was found in the lungs of a child. It resembles the 
strongylus met with in the lungs of sheep and other animals. 

STRONGYLUS SUBTILIS 

This organism has been described by Loos as being found in the 
intestines at autopsies of natives of the Egyptian lowlands. 

Annelides 

Two forms of leeches are of some pathological importance. The 
Hirudo ceylonica is a form occurring with great frequency in Ceylon 
and other islands, and in parts of South America. It is found in vegeta- 
tion, and attaches itself to the skin of the legs and to other parts of man 
by means of a sucker and its short teeth. It may give rise to painful 
ulcerations when removed. The Hirudo vorax is met with in parts of 
Europe and Africa. It gains access to the mucous membranes of the 
mouth, larynx, trachea or nasal chambers, and leads to inflammatory 
troubles. It is not able to effect a lodgment upon the skin. 

Arthropoda 

A number of parasites belonging to the groups Arachnoidea and 
Insecta are met with in man. Most of these, however, are purely 
external parasites, and are fully described in works upon diseases of the 
skin. There are two forms, however, that merit brief description here: 
the Linguatula rhinaria, its larval form of Pejitastoma tcenioides; and 
the larvae of various flies, the presence of which in the gastro-intestinal 
tract and other parts of the body is termed myiasis. 



406 



A TEXT-BOOK OF PATHOLOGY 



LINGUATULA RHINARIA 

This parasite is occasionally found in the liver, and rarely in the 
spleen, intestinal walls, lungs, and kidneys of man. It is discovered in 
small nodular lesions, which consist of the more or less degenerated 
parasite lying in a cheesy or semicalcified material, surrounded by a 
fibrous or calcareous capsule. The parasite is from 4 to 5 mm. in length 
and 1.5 mm. in breadth; has a rather rounded body, which is encircled 
by parallel rings armed with spicules; and is provided with two pairs of 
stout chitinous hooklets, one pair lying on either side of the mouth. 
The adult form, Linguatula rhinaria, resembles its larva in structure, 
but is considerably larger, the male being from 16 to 18 mm. long, the 
female from 80 to 100 mm. This form lodges in the nasal cavities and 
frontal sinuses of the dog and other animals, and produces eggs contain- 
ing the embryos, which escape with the nasal secretion and eventually 
gain access to the alimentary tract of other animals or of man. 

POROCEPHALUS CONSTRICTUS 

This species has been discovered in man in a few cases, and only 
in its larval form. It differs from Linguatula rhinaria in being larger 
(10 to 14 mm. in length) and having a smooth surface. It has been found 
in the peritoneal cavity, intestines, liver, and lungs. 

MYIASIS 

A number of flies, of the orders Estridae, Musca, Lucilia, and Sar- 
cophaga, may deposit their eggs in wounds or in cavities of the body to 
which they gain access, such as the nasal or pharyngeal chambers and 
the communicating passages. The eggs so deposited are hatched, and 
the larval insects may be retained and may occasion intense irritation. 
Sometimes the larvae are found in the gastro-intestinal tract, the eggs 
having been swallowed with food. Immense numbers may be discharged 
from the intestines, and in some cases the larvae seem to occasion intes- 
tinal irritation. The term myiasis is given to the invasion of these 
larval insects. 



CHAPTER XI 



THE METHODS OF TRANSMISSION OF THE COMMUNI- 
CABLE DISEASES 

The acquisition of a communicable or infectious disease requires 
the entrance into the animal or human body of the disease-producing 
agent, which must exist in nature in a form which can be conveyed to 
or into the body. The paths of infection have already been discussed, 
and it remains to be considered here how the viruses are brought to 
these paths. Sanitarians have supplied data which permit the classi- 
fication of the transmission of disease as direct, indirect, and through 
an intermediate host in which the virus must pass through some cycle 
of development. There are some diseases whose method of propagation 
is not yet known, and these will be discussed separately. 

The sources from which diseases are disseminated are human beings 
and lower animals. There are a few conditions, like ergot-poisoning and 
pellagra, exhibiting a clinical and pathological course much like an infec- 
tion, which seem at this time to be traceable to the vegetable kingdom. 

The diseases that pass from human being to human being far out- 
number those contracted from animals, and many are truly specific 
for man; for example, the acute exanthemata are diseases of the human 
race alone, and only very exceptionally can be transmitted experimentally 
to the lower races. As a natural corollary it follows that man is the 
greatest disseminator of infectious disease among men. Many infec- 
tions more or less specific for the lower animals are transmissible to 
man, but do not, as a rule, assume epidemic forms ; while acute infections 
peculiar to man and spread by him tend to appear epidemically or 
endemically. In like manner, animals are the most important means 
of dissemination of infection among animals. 

The transmission of disease from man to man occurs by direct con- 
tact, such as handling or kissing; indirectly, as in the use of infective 
linen, eating utensils or taking infective material into the mouth, or by 
an intermediate host, as the mosquito in malaria. 

From animals men are infected chiefly by handling or by the par- 
taking of infected milk or meat. Biting is of great importance, as 
exemplified by rabies. Man is infected by plants usually by eating, but 
simple handling of some plants, like poison ivy, produces a condition akin 
to infection in susceptible persons. Diseases are propagated among 
animals chiefly by direct contact or by infective food. When one 
animal of a herd or flock becomes infected it is easy for it to infect the 
common food supply, be it pasture, crib, or pan. The importance of 
this lies in the fact that a milk-giving herd may be infected throughout 
by one new member and render the milk unfit for human use. 

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A TEXT-BOOK OF PATHOLOGY 



Direct Infection. — Contact Infection. — This group embraces those 
diseases which demand for their dissemination a rather intimate personal 
relation of the sick and well, either by touching or the intervention of 
air or droplets in the expired air. It is doubtful if any infection is trans- 
ferred in this manner only, but certain diseases are so contracted in 
the vast majority of cases. For example, the venereal diseases — lues, 
gonorrhea, and chancroid — are practically always acquired by the intro- 
duction of the germs into skin or mucous membrane abrasions by direct 
inoculations from infected persons. Their causative organisms survive 
exposure to conditions outside the human body for a very short time. 
Drying is fatal to the SpirocJioeta pallida and the gonococcus in a few 
hours. Chicken-pox is an acute infection that seems at the present day 
only transmissible directly, that is, it is not carried by a third person. 
Rabies is a good example of direct infection, for it is obligatory that the 
fresh virus be introduced beneath the skin. While the exact means of 
transmission of leprosy is not known, it is probable that direct contact 
is necessary for its acquisition. 

Aside from these contact infections, direct transmission is air borne 
by the dissemination of bare germs or those contained in finely divided 
droplets of sputum or saliva, or carried in dust. It is to be emphasized 
that no sharp line can be drawn between direct and indirect transmission, 
because all those diseases which may be carried by fomites and food can 
be acquired by the direct passage of infective matter from the sick to 
the well. There are some infections, like diphtheria, scarlatina, mumps, 
small-pox, and measles, whose spread is possible merely through the 
air and yet can be carried by fomites and by a third person, possibly by 
a "carrier" (q. v.). These may be called the air-borne infections when 
emanations from the sick person are carried to the well merely through 
the air. The exact course of travel is not known for those diseases whose 
causative agent has not been isolated, e. g., small-pox. In the bacterial 
diseases, like tuberculosis, diphtheria, pneumonia, plague, influenza, 
micro-organisms are loosened from the patient's person by coughing, 
or the drying of secretions or excretions, and blown about by air cur- 
rents. They may settle upon surfaces, whence they are again carried 
to the well by air or contact. The most important factors in dis- 
semination of bacteria by such means are coughing and sneezing, 
which forcible expiratory actions project infective matters considerable 
distances. It is said that tubercle bacilli may be thrown twenty feet 
in front of a coughing consumptive. Few, if any, micro-organisms are 
to be found in the breath during quiet respiration. The bacteria are 
carried by droplets of sputa. These fall and dry upon surfaces, to be 
pulverized and removed by air or contact. Dust is also a carrier of germs 
and serves as a protection for them, as it keeps away light. The viruses 
of communicable diseases are for the most part quickly destroyed by 
exposure to direct light, but if protected by some envelope, as mucus 
about a tubercle bacillus, their infectivity is indefinite. Disease germs 
are common in dust and dirt that dry upon floors and walls of public con- 
veyances. In public places or conveyances, houses, hospitals, schools, 



METHODS OF TRANSMISSION OF THE COMMUNICABLE DISEASES 409 

and workshops this sputum and dust transmission is of great importance. 
Bacteria are not widely disseminated by air currents, since they soon 
perish by exposure. They are not carried far by air currents from sewers 
or drains, notwithstanding popular belief to the contrary. Bacteria 
may be propelled several feet by the bursting of bubbles in a sewer 
opening, but this is of little or no importance in the transmission of 
disease. 

Indirect Transmission. — This takes place when the agent passes 
from the sick to the well by some conveyance which permits the virus 
to grow or at least to sustain life. The vehicle may be water, food, soil, 
insects or human beings, or more passive carriers, called fomites, like 
infected bed or body clothing, towels, drinking cups, and eating utensils. 
In these transmissions we assume that the germs are simply carried by 
the vehicle as a passenger and that the vehicle itself exerts no influence 
upon them. By a prolonged existence in the vehicle and, therefore, ab- 
sence from the human body, the pathogenic organisms may become 
reduced in virulence. 

Water transmission, according to present knowledge of disease, is 
confined to typhoid, cholera, and perhaps dysentery, both of the bacil- 
lary and amebic type. No definite limit can be set for the life in water 
for the germs of these diseases, but it may be months. 

' Food Transmission. — The most important food-carrier of disease 
is milk. Typhoid fever, diphtheria, septic sore throat, and scarla- 
tina are carried by milk when contaminated during collection and dis- 
tribution by persons suffering from these diseases or by carriers. In- 
fected water used to wash cans or to dilute milk may introduce typhoid 
bacilli. Diseases originating in the animal supplying the milk, as tuber- 
culosis, foot-and-mouth disease, and Malta fever, are transmissible to 
man. The transmission of tuberculosis by milk of tuberculous animals 
cannot be doubted. 

Vegetables convey disease only when contaminated by surround- 
ings in cultivation or in the process of preparation for food. Oysters 
and other shell-fish when taken from polluted water may convey typhoid 
fever and cholera. Meat conveys animal parasites and acute bacterial 
and toxin diseases like paracolon and paratyphoid fever, botulism, and 
ptomain-poisoning. Tuberculosis is undoubtedly transmissible by in- 
fected meat. 

Soil Transmission. — There are many organisms in soil, but few of 
the varieties are pathogenic for man. Certain pathogens, like typhoid 
and plague bacilli and cocci, are occasionally to be found, but are of little 
importance in hygiene. In plague centers the soil is said to be fre- 
quently infected with plague bacilli. The organisms most frequently 
found in the soil that produce specific infections in man are those of 
tetanus, anthrax, malignant edema, and symptomatic anthrax. The 
life of these germs in soil is favored by their spore formation. 

Insect Transmission. — This may be direct or indirect. The former 
includes those transmissions in which the insect acts as an interme- 
diate host of the virus, permitting some developmental phase in it, 



410 



A TEXT-BOOK OF PATHOLOGY 



a subject to be considered later. Indirect or mechanical transmis- 
sion occurs when the insect becomes infested with human pathogens 
and carries them passively to situations where they can infect human 
beings. Thus, flies may carry typhoid bacilli upon their bodies from 
dejecta to food; fleas transfer plague bacilli from human cases or infected 
rats. There is a class of disease transmitted by biting insects in which 
it seems that the virus does not pass through a cycle of development 
in the body of the insect. The virus remains in an infective condition 
within the intermediate host for various lengths of time and may be 
transmitted to the young. In this class may be included typhus, re- 
lapsing fevers, Rocky Mountain fever, and trypanosomiasis. It may be 
found later that a cycle of development occurs in these insect bearers. 

Animal Transmission. — Animals may act as passive carriers of such 
diseases as diphtheria, scarlet fever, or measles by association with in- 
fected persons. The cat is one of the commonest of such conveyors; it 
is frequently responsible for the spread of the mycosis favus. Animals 
act as active carriers of various worms. Certain diseases, like actino- 
mycosis, may be transmitted to man by animals. 

Human Transmission. — Human beings transfer infection in one of 
three ways: (a) when actively suffering from disease; (b) passively from 
sick to well upon person or clothing, and (c) as "carriers." The opera- 
tion of the first and second methods is obvious; it is to be understood 
that under the second heading the conveying person is not ill with 
the disease he is transmitting. "Carriers" are persons who having 
suffered with a disease have not destroyed or discharged all the virus 
from the body when recovery took place. This virus has remained in 
some locality protected from the action of the blood-serum, or by long 
sojourn in the body has become immune or "fixed" or "fast" to the 
bodily defenses. Under certain circumstances it may leave the body 
and infect others. Thus, after typhoid fever, typhoid bacilli may re- 
main in the alimentary tract for years, passing out with feces and con- 
taminating surroundings or the water and food supply. This also 
occurs after cholera and diphtheria; in the latter case Klebs-Loffler 
bacilli remain in the throat a long time. These persons might be 
called "chronic carriers," while the persons' who merely passively 
transfer infection might be termed "accidental carriers." During an 
infectious disease the patient is, of course, a carrier, and might be spoken 
of as an "infected carrier." 

Transmission by inanimate objects or fomites is purely mechanical. 
It is of importance in all infectious diseases except those only transferred 
by insects. 

Insect Transmission with a Cycle of Development in the Interme- 
diate Host. — This is a group differing from the indirectly insect-borne 
diseases, in that a period of time must elapse between the reception of 
the virus in the body of an insect until it becomes infective for man. 
The diseases whose transmission by this means seems now proved beyond 
doubt are malaria, yellow fever, filariasis, and dengue. Mosquitoes are 
the "intermediate host" and man is called the "definitive host." Ticks, 



METHODS OF TRANSMISSION OF THE COMMUNICABLE DISEASES 411 

flies, and other insects also transmit disease and may permit some 
form of development, but this is not yet proved. 

Despite the fact that in all insect-borne diseases the viruses do not 
have the same biological history, there are many analogies among them. 
The insects concerned are biting or suctorial, and include mosquitoes 
carrying the viruses above mentioned; ticks, transmitting relapsing 
fever, Rocky Mountain fever, and tick fever; flies, transmitting trypano- 
somiasis; and lice, believed to convey typhus. 

The viruses of yellow fever, dengue, and the tick fevers have not 
yet been isolated, but epidemiologically their connection with insects 
is well established. The insect transmitting African relapsing fever is 
known, but the other forms are still in doubt. (See page 339.) 

These insect-borne diseases are transmitted always by the same 
species of intermediate host, and the virus seems specific for species in 
the definitive host. One insect seems to carry only one form of virus. 
The contagium does not harm the carrier so far as known. The diseases 
appear only where their respective insects live, and when they spread 
it is the definitive host which carries them, since the insects do not 
travel far. These infections are not directly communicable. There is 
a definite and quite constant incubation period peculiar to each disease 
for both the intermediate and definitive host. Ticks are the only 
ones that transfer the virus to their young. 

Method of Transmission Unknown. — In this class only one disease is 
of importance — poliomyelitis. This acute infection appears and spreads 
in a manner which baffles investigation. The following theories have 
been offered to explain the spread of infantile paralysis: 

1. That it is passed from person to person via the nose and throat, 
these localities being constant seats of the virus and the most probable 
infection atrium; that it is carried in the nose or upon the person by 
hidden or abortive cases or by an accidental carrier. 

2. That it resists conditions outside the body long enough for it to 
pass through the air long distances, and to remain virulent in dust. 

3. That it is transmitted by insects. Rosenau showed that the 
disease can be transmitted from monkey to monkey by the bite of the 
stable fly (Stomoxys calcitrans). 

None of these theories cover all cases. It is certainly not easily 
transmitted by direct contact, because frequently only a single member 
of a large family of children may be affected. 



PART II 
SPECIAL PATHOLOGY 



CHAPTER I 
DISEASES OF THE BLOOD 
ANATOMY 

The blood is a liquid tissue composed of corpuscles or cells and a 
fluid intercellular substance. The cells are of three kinds: the red 
corpuscles, or erythrocytes; the white corpuscles, or leukocytes; and the 




) 



Q 



Fig. 170. — Unstained red blood-cells, showing rouleaux formation. (Picture prepared 
under direction of C. Y. White.) 

hlood-plaques, or platelets. The fluid element of the blood, the liquor 
sanguinis, or plasma, is an albuminous and saline liquid of a slightly 
varying composition. The blood as a whole is red in color, rather viscid, 

412 



DISEASES OF THE BLOOD 



413 



and alkaline to ordinary indicators, though actually neutral in reac- 
tion. The total quantity is about one-thirteenth of the body-weight. 

The erythrocytes, or red corpuscles, are biconcave disks averag- 
ing 7 /j, in diameter and having a yellowish or amber color. They are 
quite uniform in size and regularly rounded. Histologically they are 
composed essentially of an albuminous substance containing hemoglobin 
embedded in a delicate stroma. The hemoglobin is the important ele- 
ment, and constitutes about 95 per cent, by weight of the corpuscles. 
In early fetal life most of the red corpuscles are nucleated, but the nu- 
cleated forms later decrease in number and are comparatively scanty at 
the time of birth. Within the first few months of postfetal life all of 
them disappear, and in subsequent years nucleated corpuscles are 




Fig. 171. — Unstained red blood-cells, showing crenation and similarity to sporulating 
malarial Plasmodia. (Picture prepared under direction of C. Y. White.) 

present only in cases of disease. According to some recent investiga- 
tions it would appear that the red cells of adult human blood always 
contain nuclei demonstrable only by certain staining methods. The sup- 
posed nuclei shown in some of these methods are certainly artefacts. 
As to others, further investigation is needed. 

There are about 5,000,000 red corpuscles in the cubic millimeter of 
the blood of normal individuals. The figures vary slightly at different 
times in the same individual, and many influences contribute to the 
production of more lasting changes in number (see pp. 420, 431). The 
volume of the red corpuscles in a given bulk of blood is dependent upon 
their number and their size. Observers have reached varying results in 



414 



A TEXT-BOOK OF PATHOLOGY 



studying the volume, but it may be placed at between 40 and 50 per 
cent, of the total bulk of the blood. 

Skeined Cells. — The method of vital staining that has been recently 
introduced discloses certain varieties of erythrocytes that have excited 
discussion. A drop of blood is mixed with oxalated sodium chlorid solu- 
tion, to which brilliant cresyl-blue has been added. The sedimented 
red corpuscles are then placed under a cover-glass and examined. 
A certain proportion of the erythrocytes are found to present a skeined 
or reticulated appearance, which is due to the presence of granules con- 
nected by fine threads or a variously arranged network of threads or 
granules stained by the coloring-matter used. These cells have been 
regarded by some as degenerative forms, but are more probably young 
cells. In various anemias in which active hemogenesis is going on the 
skein cells are more abundant than in normal blood. 

The leukocytes, or white corpuscles, are rounded or spherical 
bodies presenting a more or less granular appearance in the fresh state. 
They vary in size from the diameter of the red corpuscles to several 
times the size of the latter. There are several more or less distinct 
varieties of leukocytes, but as transitional forms occur classification is 



Fig. 172. — Unstained leukocytes. 



difficult (Fig. 172). The terminology introduced by Ehrlich is still in 
quite general use, though recent authorities have disputed many of his 
views regarding the relationship and source of different forms. Refer- 
ence will be made to these points in the discussion of the origin of leu- 
kocytes. 

Ehrlich distinguished the following forms in normal blood: (1) 
Lymphocytes; (2) large mononuclear; (3) transitional; (4) polymorpho- 
nuclear, and (5) eosinophiles. A sixth form, basophiles, may be added, 
though they occur in only very small numbers in normal blood, and when 
in larger proportions signify pathological conditions (Fig. 173). 

1. Lymphocytes. — These are, on the average, about the size of red 
corpuscles, some a little larger, others smaller; they are spherical in 
shape and contain a relatively larger round nucleus surrounded by a 
narrow band of protoplasm often so slight that it is scarcely visible. 
The nucleus is rich in chromatin, staining deeply with basic stains, and 
containing one or two nucleoli. Occasionally it is oval or slightly in- 
dented on one side. The protoplasm is slightly basophile and with 
Giemsa or Leishman's stain may present somewhat sparse, fine or coarse 
granules (azur granulation). The lymphocytes constitute 20 to 25 per 
cent, of the normal leukocytes. 



DISEASES OF THE BLOOD 



415 



2. Large Mononuclear Leukocytes. — These are called by some 
"large lymphocytes," and, undoubtedly, with certain stains a distinction 
between the larger forms of lymphocytes and certain large mononuclear 
forms is impossible. The size varies from 15 to 25 fx; the cell is ovoid 
and contains a rather large (7 to 10 /j.) round nucleus which is relatively 
poor in chromatin, so that in the stained blood it is much paler than that 
of the lymphocyte. There is no nucleolus. The protoplasm is feebly 
basophile, with only occasional granulation (azur granules). The clear 
non-granular character of the protoplasm has suggested the term 
"hyaline cell." 

3. Transitional Leukocytes. — These are similar to the last, but 
differ in that the nucleus is indented or somewhat irregular in outline. 
It is very often impossible to determine satisfactorily whether a certain 
cell is a large mononuclear or a transitional form, and the two may be 




Fig. 173. — Various forms of blood-corpuscles: a, Lymphocyte; 6, lymphocyte approach- 
ing c; c, large mononuclear; d, transitional; e, polymorphonuclear neutrophile; /, poly- 
morphonuclear eosinophile; g, broken eosinophile; h, neutrophilic myelocyte; i, eosino- 
philous myelocyte;/, basophile mast-cell; k, red corpuscles; I, nucleated red corpuscles. 

considered as practically the same. The protoplasm may be free of 
granules, or may present fine neutrophilic granulation. The large 
mononuclear and transitional forms together make up 4 to 8 per cent, 
of the normal leukocytes. 

4. Polymorphonuclear Leukocytes; Polynuclear Leukocytes; Neu- 
trophiles. — These are the most numerous forms. They are somewhat 
smaller than the large mononuclear elements, being from 10 to 12 ^ 
in diameter, and are distinguished by a polymorphous nucleus which 
is richer in chromatin than that of the large mononuclear form, though 
less rich than that of the lymphocyte. The nuclei are elongated and 
variously curved or distorted, so as to resemble the letters S. U, V, Z. 
etc., and in some cases they are wreath shaped. Frequently, parts of 
the nucleus are so thin that they are scarcely visible, or actually be- 
come broken, and the term "polynuclear" was, therefore, applied. 
This name is, however, less accurate than the term "polymorphonu- 



416 



A TEXT-BOOK OF PATHOLOGY 



clear." The amount of chromatin in the nucleus varies greatly, and 
the size of the nucleus is correspondingly variable. The protoplasm 
usually contains fine granules, which are closely set and almost com- 
pletely fill the cell. These granules have a strong affinity for neutral 
mixtures of anilin or other stains, especially for the triacid stain, and 
have, therefore, been called the neutrophilic granules (see p. 418). 
The polymorphonuclear neutrophiles constitute 60 to 70 per cent, of 
the normal leukocytes. 

5. Eosinophiles. — These are slightly larger than the polymorpho- 
nuclear neutrophiles, their nuclei are polymorphous, though not so 
much divided and not so basic in staining affinity as the nuclei of the 
neutrophile. The protoplasm contains large granules which stain in- 
tensely with acid stains. In pathological conditions certain other cells 
containing eosinophile granules are met with (see Myelocytes). They 
constitute 1 to 4 per cent, of the leukocytes of the normal blood. 

6. Basophiles. — These are polymorphonuclear cells the nucleus of 
which stains poorly with basic stains. The protoplasm contains irregu- 
lar sized granules of intense basic affinity. About 0.5 per cent, of the 
leukocytes of the normal blood are of this type. 

Pathologically, certain other forms of cells of the leukocyte series 
occur in the blood. Among these are: (a) Myelocytes, (b) plasma cells, 
and (c) leukoblasts. Occasionally myeloplaxes, or marrow giant cells, 
are present. 

(a) Myelocytes. — These are large cells identical with the large 
granular cells of the bone-marrow. They are often three or four times 
the size of the red corpuscles, and are distinguished by a large, pale, 
oval nucleus generally placed close to one side of the cell. The proto- 
plasm is sometimes entirely free of granulations, but usually contains 
fine neutrophile granules. Eosinophile and basophile myelocytes are 
less frequent, but are sometimes seen in fairly considerable numbers in 
leukemia. The nucleus is frequently somewhat irregularly outlined, 
and not rarely suffers degenerative change. Smaller cells, resembling 
the typical myelocyte in the character of the nucleus and protoplasm, 
are sometimes observed, and are difficult to classify. Myelocytes occur 
in exceedingly small numbers, if at all, in normal blood. They are abun- 
dant in certain forms of leukemia, and also occur in pernicious anemia 
and various infectious and systemic diseases. 

(b) Plasma Cells, Stimulation Cells, Irritation Cells (Tiirck). — 
These are oval cells, varying in size from 5 to 15 fx in diameter; and 
contain an eccentrically placed round or oval nucleus. Both nucleus 
and cytoplasm are decidedly basophile, especially the latter. There 
are no true granules, but the deeply stained cytoplasm often presents an 
indefinite granular appearance. Great variation in the character and 
staining reactions have been noted by different investigators, and an 
accurate definition is, therefore, difficult. 

(c) Leukoblasts. — In various blood diseases, especially in acute leu- 
kemia, there are found certain spherical cells varying in size from 8 to 
20 in diameter, and containing a large, somewhat eccentric nucleus, 



DISEASES OF THE BLOOD 



417 



poor in chromatin, and a non-granular cytoplasm. These cells have 
been regarded as large lymphocytes or as non-granular myelocytes, 
but are now more generally considered as primitive or mother-cells of 
the leukocyte series, and have, therefore, been named leukoblasts, 
myeloblasts, primordial cells, etc. 

(d) Myeloplaxes, or megakaryocytes, are large cells, sometimes 
several times the size of myelocytes, containing a large, highly poly- 
morphous nucleus, and a moderately granular cytoplasm. These cells 
are occasionally found in the circulating blood in severe anemias. 

The granules of the leukocytes are classified according to their 
behavior with the anilin stains. Ehrlich distinguished four important 
types of granules (Fig. 174). 




c 

d 



Fig. 174. — Leukocytes, showing various forms of granulation: a, Neusser's basophilic 
perinuclear granules; 6, large mononuclear cells with 5-granules; c, mast-cell granules; 
d, basophilic lymphocytes, 5-granules; the stain in b, c, and d was a mixture of eosin and 
hematoxylin, the cover-glass being kept in the stain several hours at 37° C. (98.6° F.). 

(1) a-Granules, Eosinophile Granules, or Oxyphile Granules. — 

These are coarse granules giving the appearance in the unstained blood 
of minute fat-droplets; they are highly refractive, and have been shown 
to be composed of albuminous material. They are distinguished by their 
strong affinity for acid stains, and in particular for eosin. This circum- 
stance has given rise to the names eosinophile and oxyphile (Fig. 175). 

The eosinophile granules in the normal blood occur only in poly- 
morphonuclear leukocytes. 

(2) ^-Granules ; Mast-cell Granules. — These are intensely basophilic, 
coarse granules, occurring in mononuclear cells. The mast-cell is 
identical with Waldeyer's plasma-cell of the tissues. It is present in 
small proportions in the normal blood (Fig. 174). 

(3) ^-granules are fine basophilic granules occurring in the lympho- 
cytes or large mononuclear cells (Fig. 174). 

27 



418 



A TEXT-BOOK OF PATHOLOGY 



(4) £-Granules; Neutrophilic Granules. — These are the most abun- 
dant and the most important of all the forms. They occur as fine granu- 
lations, filling up the protoplasm of the polymorphous cells, and they 
are occasionally present in transitional leukocytes. They are dis- 
tinguished by their affinity for the neutral mixtures of Ehrlich (Fig. 175), 
It must be recognized, however, that these granules are, in reality, faintly 
oxyphilic, receiving the acid stains, such as eosin or acid fuchsin, more 
readily than basic stains. 

In recent years by newer methods (Leishman, Giemsa) a special 
form of granule, "azur-granules," has been distinguished and has been 
regarded as highly significant, especially of cells of the lymphocytic 
series. This view, however, is far from being established. Not im- 
probably immature granules of myeloid cells also present this staining 
reaction. 

Altmann and, later, Schridde and others have described certain 
fuchsinophile extranuclear granules which are regarded by some as 



Fig. 175. — Blood in lienomedullary leukemia, showing several mononuclear neutro- 
philes (myelocytes), one polymorphonuclear neutrophile, and an eosinophile; a nucleated 
red corpuscle and a lymphocyte are seen in the lower part of the illustration; stained with 
Ehrlich's triple mixture. 



highly characteristic of the lymphocytic series of cells. The significance 
of these granules is still very uncertain. 

The nature of the granules of the blood is still obscure. They are un- 
undoubtedly connected in some way with the specific function of the 
leukocytes, but whether they are specific cellular secretions (Ehrlich) 
or essential anatomical structures (Altmann) is unknown. 

The number of leukocytes in the normal blood varies considerably. 
The average number, however, is between 6000 and 8000. Alterations 
in the number under various circumstances will be discussed later. 

Proportions of the Different Forms. — The relative proportions 
("differential count") of the different leukocytes are determined by 
counting large numbers and calculating the percentage proportion of 
each form. Approximately there are 20 to 30 per cent, lymphocytes, 
60 to 70 per cent, polymorphonuclear forms (neutrophiles and eosino- 




DISEASES OF THE BLOOD 



419 



philes), 4 to 8 per cent, transitional and large mononuclear. About 1 to 
3 per cent, of all the leukocytes contain eosinophile granules, and occa- 
sionally a larger proportion is met with in normal blood. About 0.5 per 
cent, of the normal leukocytes are basophilic. 

Blood=plaques or Platelets.— These are small disks somewhat re- 
sembling the red corpuscles, though smaller and without the character- 
istic biconeavity of the latter. They contain a chromatic body and have 
been described as nucleated by some observers. They rarely exceed 
3 ji in diameter, and are often much less. They are viscid, and tend to 
adhere to the other corpuscles or to become agglutinated in clusters. 
The total number has been estimated at from 150,000 to 500,000 per 
cubic millimeter. The origin of the platelets is still uncertain. Accord- 
ing to some they are derived from the erythrocytes by a process of ex- 
trusion from the cytoplasm of the latter; others have held that they are 
formed by the breaking down of leukocytes. Wright claims to have 
shown that they are products of the megakaryocytes of the bone- 
marrow. 

The plasma of the blood is an albuminous liquid containing mainly 
serum-albumin and serum-globulin and various saline compounds. The 
relative proportion of serum-globulin to serum-albumin is as 1 to 1 or If. 
Of the saline constituents, sodium salts are most important, the phos- 
phates, carbonates, sulphates, and chlorids being most abundant. 
Various other nitrogenous and non-nitrogenous substances are present 
in small proportions. Reference will be made to some of these below. 

BLOOD FORMATION 

The process of blood formation is still a matter of uncertainty in 
some particulars. The prevailing opinion is that all of the blood-cor- 
puscles, erythrocytes and leukocytes, are derived from mesoblastic 
cells which become differentiated to form the lining endothelia of blood- 
vessels and lymphatics. From the former group the primitive cells 
which give rise to erythrocytes and the granular leukocytes take their 
origin; from the lymphatic endothelia are developed the primitive cells 
which originate the lymphocytic series. The earliest clearly differen- 
tiated blood-cell is a large hemoglobin-containing cell with pale nucleus, 
found in the mesoblastic columns in which the blood-vessels are differ- 
entiated. This is the primitive erythroblast. According to older in- 
vestigators the erythroblasts were derived from this cell. More recent 
investigations, however, seem to show that this is but a temporary 
phase in fetal blood formation. Later, the endothelia of the blood- 
vessels give rise to (1) certain basophilic erythroblasts, containing no 
hemoglobin, from which the red cells are derived; and (2) myeloblasts 
from which the myelocytes and their derivatives take their origin. The 
lymphocytic series, by a similar process of differentiation, is derived 
from the endothelia of lymphatic channels. 

During the earlier portion of fetal life the liver is the principal seat 
of blood formation; after the third month the spleen and bone-marrow 



420 



A TEXT-BOOK OF PATHOLOGY 



participate, but the spleen ceases to be active somewhat before the end 
of fetal life and the liver shortly after birth. The lymphatic glands are 
the chief source of lymphocytes in intra- and extra-uterine life. It is 
noteworthy that in many anemic conditions a return to fetal processes 
of blood formation is observed. 

PATHOLOGICAL CHANGES IN THE RED CORPUSCLES 

The size of the red corpuscles varies in diseases of different kinds. 
The term anisocytosis has been suggested for this irregularity. There 
may be dwarf corpuscles, 2 to 4 or 5 /jl in diameter (microcytes) ; or, on 
the other hand, giant cells (megalocytes) , from 9 to 15 n or even 20 fi in 
diameter. The small forms frequently have a spherical shape rather 
than the disk-like form of the normal corpuscle, and may be deeply pig- 
mented. The large corpuscles are often irregular in shape, and are 



Fig. 176. — Blood from a case of pernicious anemia: a, Megalocytes; b, microcytes; c, poi- 
kilocytes; d, nucleated erythrocytes; e, normal erythrocytes;/, leukocytes. 



prone to be paler and more basic than normal corpuscles, and usually 
appear without the concavity of the normal cell (Fig. 176). Some ob- 
servers have found that the average size of the red corpuscle is greater 
in certain diseases than in health. This is sometimes the result of hy- 
dropic conditions. 

The shape of the corpuscles often suffers great change, and many 
forms of irregularity may be observed. The term poikilocytosis is ap- 
plied to this condition (Fig. 176). Some of the poikilocytes may be ex- 
ceedingly small and may present active movements. These have been 
termed "pseud obacilli" by Hayem. These changes of form in red cor- 
puscles are regarded by many authorities to be the result of degenerative 
changes in the protoplasm with consequent ameboid movement which 
occasions irregular projections. The small forms are doubtless in many 
cases the result of fragmentation. Ehrlich used the term "schistocyte" 
to indicate this fact 




/ 



DISEASES OF THE BLOOD 



421 



Dust=corpuscles. — Muller described certain small spherical bodies 
somewhat resembling the leukocytic granules, but lying free in the 
plasma and often actively motile. These he termed hemokonice, or 
dust-corpuscles. They occur in normal blood as well as in that of 
various diseases. A number of theories have been offered regarding the 
nature of these bodies. Some authors regard them as extruded leukocytic 
granules; others, as portions of protoplasm of the leukocytes. Our own 
belief is that they are fragments of red corpuscles, similar to those that 
may be produced by heating fresh blood under a cover-glass to destruc- 
tive temperatures. Under these circumstances small, bud-like processes 
are formed on the periphery of the red corpuscles, and some of these 
may break off and float free in the plasma. 

Visible ameboid movements may sometimes be observed under 
the microscope, especially in severe anemias, such as pernicious anemia. 

Nucleated Red Corpuscles, or Erythroblasts. — The red corpuscle 
when first formed is always nucleated, and throughout fetal life a dimin- 
ishing proportion of the erythrocytes remains so. At birth and through- 
out extra-uterine life the erythrocyte is non-nuclear. The loss of the 
nucleus was formerly attributed to a process of extrusion, but is now 
believed to be always due to pyknosis, karyorrhexis, and karyolysis 
within the cell. 

Nucleated erythrocytes occur in the severe anemias as in fetal blood. 
They are more frequent in the severest cases, and in particular in the 
anemias of children. Some are exceedingly small (microblasts) , some 
about the size of the normal red corpuscle (normoblasts), and some 
large and irregular (megaloblasts) . The stained nucleus of the normo- 
blast is darker and more compact than that of the megaloblast, and is 
often near the periphery of the cell or apparently partly extruded. The 
smaller forms appear first and in the more moderate anemias; occa- 
sionally they occur in great numbers or crops from time to time (blood 
crises). Degenerations of nucleated red corpuscles may occur, and very 
frequently are seen in the circulating erythroblast. The usual forms 
are karyolysis — solution of the chromatin; karyorrhexis — fragmenta- 
tion of the nucleus; and pyknosis — clumping or condensation of the 
nuclear structure. Granular degeneration, vacuolation, and nuclear 
atrophy also occur. 

Karyokinetic figures are occasionally seen in the.nuclei of erythro- 
blasts, in pernicious anemia, in leukemia, in dibothriocephalus anemia, 
and in certain anemias of children. 

Shadow corpuscles are red corpuscles that have lost their color 
almost completely and are scarcely visible. They may be observed in 
severe anemias, and especially in cases of intoxication with blood- 
poisons. 

Ring Bodies. — Cabot, by means of Wright's modification of Leish- 
man's stain, has demonstrated in the red cells of anemic blood the 
presence of ring bodies, which he is inclined to believe represent the 
remains of a previously existing nucleus. They were found in 3 cases 
of pernicious anemia, 3 of lead-poisoning, and 1 of lymphatic leukemia, 



422 



A TEXT-BOOK OF PATHOLOGY 



in all of which normoblasts were also found. The rings appear to be 
made up of a series of granules in some cells; in others, of a continuous 
line. They usually stain red, though blue is not uncommon. 

Polychromatophilia. — The normal red corpuscle has a special 
affinity for acid stains. In diseased conditions it may develop an 
affinity for basic stains, and when colored with mixtures of acid and 
basic stains may present tints combining all the stains employed. Thus 
in staining with eosin and hematoxylin the degenerated corpuscles may 
present a purplish or violet color, instead of a pink. 

Vacuolation and pigmentation of the red corpuscles are rare forms 
of degeneration. The pigmentation is due to separation of the hemo- 
globin in the form of irregular granules. 

Basic degeneration is a form of degeneration in which minute or 
rather coarse granules that stain with certain basic stains are found in 
the substance of the red corpuscles. The number of granules in the 
cell may be small or large; the cell may be otherwise little altered; it 
may be polychromatophilic. The condition has been found in various 
diseases, such as leukemia, pernicious anemia, and malaria, but is most 
frequent in lead-poisoning. Some observers, by using certain special 
staining methods, claim that the basic granules are nuclear fragments 
and regard the process as regenerative rather than a degeneration. 
It is very probable, however, that the granules seen in these studies 
have not been those now under discussion. 

Alterations of Isotonicity. — All forms of cells have certain osmotic 
relations, in consequence of which they retain their constituent elements 
in the presence of surrounding liquids of certain osmotic tension. If the 
osmotic relations vary or the surrounding liquids are altered, the constitu- 
ents of the cell may be extruded. In the case of blood-corpuscles distilled 
water rapidly abstracts the hemoglobin and other substances, but saline 
solutions of certain strengths do not so affect the corpuscle. The exact 
strength of a certain saline solution may be determined which will pre- 
serve the corpuscle, and this is known as the isotonic strength of the 
corpuscle expressed in percentage terms of the saline used. Degener- 
ated corpuscles more readily yield their constituents, and the isotonic 
saline solution is, therefore, of higher percentage. In normal blood 
the isotonicity of the red corpuscle is generally 0.46 to 0.48 per cent. 
NaCl; that is, solutions of common salt of this strength do not affect 
the red corpuscles. In certain anemic diseases the isotonic solutions 
may be from 0.5 to 0.6 per cent., but often, on the contrary, solutions 
from 0.40 to 0.44 per cent, may be isotonic. 

PATHOLOGICAL CHANGES IN THE LEUKOCYTES 

Very frequently degenerations of the nuclei of the leukocytes are 
observed in the form of fragmentations or karyolytic change. Atten- 
tion has been called (Neusser) to the presence of basophilic granules 
about the nucleus in certain forms of disease, such as leukemia, gout, 
and lithemia in its widest sense. These granules are supposed to be sig- 



DISEASES OF THE BLOOD 



423 



nificant of disintegration of the nuclei in the process of uric-acid forma- 
tion. Their nature and significance, however, are unsettled. Occa- 
sionally vacuolization and fatty degeneration of leukocytes are observed, 
and sometimes, as in infectious fevers and in suppuration, glycogen may 
be found in abnormal quantities. In cover-glass preparations the leuko- 
cytes are sometimes found broken or fragmented; or fenestrated, basket- 
like, pale-staining forms are seen. The latter doubtless occur to some 
extent in the circulating blood and are frequently spoken of as "leuko- 
cytic shadows." , 

Iodophilia. — This term is applied to a condition of the blood in 
which there are found in the leukocytes or the plasma granules that 
stain with iodin, like glycogen. The term "glycogenic reaction" was 
formerly applied, though recently some question has arisen as to the 
glycogenic nature of the granules in question. The leukocytes involved 
in this form of granulation are chiefly the polymorphonuclear. Baso- 
philic leukocytes may be affected, but never the eosinophiles. The 
intracellular material is found in the form of small granules of regular 
shape and size, which stain a yellowish-red or brown color with iodin. 
Less commonly the leukocytes may be diffusely stained, the granules 
being wanting or so small as to be indistinguishable as granules. The 
extracorpuscular granules are found in more advanced cases. They 
resemble the intracorpuscular granules in appearance. 

The significance of iodophilia has not been positively determined. 
The condition is found in association with leukocytosis or less com- 
monly in the absence of leukocytosis, but it bears no quantitative rela- 
tion to the degree of leukocytosis. It has been found in various forms of 
toxemia, in grave anemias due to loss of blood or to other causes, in 
fevers, and in various other conditions. 

The blood-film, without previous fixation, is stained with iodin and 
iodid of potash in a gum-arabic solution. 

PATHOLOGICAL CHANGES IN THE PLASMA 

Various disorders of the plasma have been studied. These are 
mainly of a chemical sort, and consist of the presence of abnormal 
substances or of normal constituents in excessive quantity. Urea 
is present in large quantities in some cases of nephritis and uremia, and 
older authorities believed the symptoms of uremia due to the presence of 
this substance. This view is no longer held. Uric acid occurs in small 
quantities in health; but in larger quantities in gout, leukemia, in some 
forms of leukocytosis, and other disorders of the blood. Sugar is found 
in excessive quantities in diabetes, in cases of high blood-pressure, in thy- 
roid diseases, and, according to some observations, in*cases of carcinoma. 
Levulose and other carbohydrates are rare constituents of the plasma. 
Fatty acids may be present in leukemia, diabetes, acute yellow atrophy 
of the liver, and some other diseases. The quantity of sodium in the 
plasma increases in anemic diseases. 

Certain changes occur in the plasma or serum in certain anemic dis- 
6£lSCSj clS Si result of which the globulicidal character is increased. The 



424 



A TEXT-BOOK OF PATHOLOGY 



nature of these changes is obscure. The presence of toxic substances 
the result of bacterial action is referred to in the discussion of bacteria. 

Hypertonicity of the serum is a term indicating that the salinity of 
the plasma or serum is such that the blood may be somewhat diluted 
without destruction of the corpuscles. By graduated dilutions the de- 
gree of hypertonicity may be estimated, and is found less in certain 
diseases than in health. (See Isotonicity of the Red Corpuscles.) 

Hyperinosis and hypinosis are terms designating increased and 
decreased capability for fibrin formation. The former is met with at 
times in chlorosis, leukemia or other anemic affections, and in certain 
infectious diseases. The latter is notably present in leukemia, perni- 
cious anemia, and some cases of hemolysis. There has been much 
theorizing in regard to these conditions, but very little knowledge of 
practical importance has been acquired. 

PLETHORA 

This is the name applied by the older writers to a condition in 
which the total quantity of blood was supposed to be excessive. It is 
now recognized that plethora is much less frequent and permanent than 
was formerly believed. Several varieties were described. 

Plethora vera was the name given to the condition in which the 
quantity of the blood was supposed to be increased without change in 
its quality. Persons supposed to have this condition are described as 
robust, with high color and vigorous circulation. They are generally 
individuals living in luxury. The term "full-blooded" is still applied, 
but it is recognized that the fulness of the superficial vessels is the 
result of peculiarities of the circulation rather than of increase in the 
quantity of blood. 

Plethora apocoptica is the term given to conditions in which there is 
local increase in the blood. 

Plethora hydremica is a condition in which the total quantity of the 
blood is increased by dilution. This was regarded as frequent in cases 
of cachexia, after hemorrhages, etc. 

Experimental evidence might be referred to to substantiate the view 
that plethora in the strict sense does not often occur as a lasting condi- 
tion. Temporary plethora is produced by the drinking of large quanti- 
ties of liquid, but the excretory organs soon dispose of this excess. 

OLIGEMIA 

This is a term indicating reduction in the quantity of blood. This 
is met with temporarily after hemorrhage, but very soon serous liquid 
from the tissues enters the blood-vessels and restores the original 
quantity. At the time of the hemorrhage the quantity may be imme- 
diately reduced to a very great degree without causing death. Serious 
consequences are averted by the activity of the vasomotor system, the 
blood-vessels accommodating themselves by contraction to the reduced 
quantity of blood. Subsequently when liquid of the tissues is absorbed 
into the blood-vessels the latter dilate and their natural volume is soon 



DISEASES OF THE BLOOD 



425 



restored. The blood, however, becomes hydremic, or watery. Oli- 
gemia or quantitative anemia may possibly occur in certain cachectic 
and anemic diseases, but this has not been proved, and the relative 
proportion between the mass of blood and the weight of the body is 
certainly not much disturbed in any case. 

HYDREMIA AND ANHYDREMIA 

Hydremia, a diluted or watery condition of the blood, may occur 
from excessive consumption of water, but active excretion of liquid 
soon restores the blood to its previous condition. Hemorrhage leads to 
hydremia in the manner above described; and in the chronic anemias 
there is possibly some dilution of the serum. It has never been shown, 
however, in any of the many experiments made to determine this point 
that the plasma in anemias is less rich in solid consituents than normal 
plasma. The reduction in solid matter in the blood as a whole is due to 
the diminution in the number of red corpuscles and changes in their 
composition. 

Anhydremia is a condition in which the plasma of the blood is 
thickened by the loss of watery elements. This may occur in con- 
sequence of excessive sweating or excessive discharge of water from the 
bowels, kidneys, etc. The number of red corpuscles in a given bulk of 
blood increases. The specific gravity and the solid residue of the blood 
as a whole increase correspondingly. 

LIPEMIA 

This is a pathologic condition in which fat occurs free in the blood- 
plasma. Fat is always present as a normal constituent of blood, and 




pi g _ 177. — Blood from a case of lipemia, stained with osmic acid: upper half of field 
cleared with oil of turpentine; lower half shows the fat-droplets and granules stained 
with osmic acid between the blood-corpuscles; enlargement, 100 diameters (after Gum- 
precht; Deutsch. med Woch., Sept. 27, 1894). 



426 



A TEXT-BOOK OF PATHOLOGY 



is in slight excess during the process of digestion. Lipemia occurs in 
cases of chronic nephritis, diabetes, pulmonary tuberculosis, alcohol- 
ism, and some other conditions, and may reach marked grades of sever- 
ity. The blood may have a milky appearance to the naked eye, and 
under the microscope highly refractive droplets or granules are observed. 
The latter stain black with osmic acid (Fig. 177). 

The appearance of fat in the blood is ascribed by some to an altera- 
tion in its character when being transported and to a decrease in tissue 
and blood lipase. It may appear in conditions of reduced nutrition 
when the fat is transferred from fat depots to other situations for 
metabolic use. 

MELANEMIA 

This condition is distinguished by the occurrence of dark pigment 
or granular matter in the circulating blood. It occurs in cases of malaria 
and certain other fevers. The pigment may be free in the plasma in the 
form of yellowish or blackish granules; or may be found as small par- 
ticles in the leukocytes. 

HEMOCYTOLYSIS— HEMOGLOBINEMIA 

Definition. — Hemocytolysis is the term applied to the conditions 
in which the red blood-corpuscles are destroyed. The name hemolysis 
is generally employed in the same sense, though it refers to destruction 
of all of the elements of the blood. In this condition hemoglobin is 
liberated and is dissolved in the plasma. To this the term "hemoglobi- 
nemia" is applicable, but the name "methemoglobinemia" is more ap- 
propriate, as the hemoglobin is usually present in the serum in this 
altered form. 

Etiology. — Hemolysis constantly takes place in the liver, the 
coloring-matter of the blood being converted into bile-pigments. Path- 
ological hemolysis results from the action of various infectious and toxic 
agents. It occurs in the course of severe malaria, relapsing fever, pneu- 
monia, and various hemorrhagic infections; and is occasioned by many 
poisons (see Blood-poisons). Excessive cold may be a contributing 
cause, as seems to be the case in some instances of paroxysmal hemo- 
globinuria (q. v.). 

The serum of certain animals has more or less hemolytic effect when 
injected into other animals. By repeated injections the serum of the 
animal under experiment may acquire hemolytic properties. Anti- 
hemolysins have also been produced in experimental investigations and 
promise to be of practical use, as in the case of certain hemolytic venoms. 
The explanation of hemolysis elaborated by Ehrlich and later con- 
firmed by Flexner and Noguchi is referred to in the section on Immunity. 

Pathological Anatomy. — The blood may present striking morpho- 
logical changes in the red corpuscles, such as microcytosis, megalocy- 
tosis, poikilocytosis, fragmentation, and vacuolation. Shadow cor- 



DISEASES OF THE BLOOD 



427 



puscles may be abundant, and in the later stages of the process begin- 
ning regeneration of the blood causes the presence of nucleated red cor- 
puscles. The blood as a whole is often quite dark in color. 

Associated changes are frequently met with in the liver, kidneys, 
and skin. The hepatic cells are often swollen and more or less degener- 
ated and bile stained. Excessive production of bile (polycholia) may 
occur. This overproduction, with the swelling of the hepatic cells and 
the consequent obstruction of the biliary channels, occasions reab- 
sorption of bile and consequent jaundice (so-called "hematogenous jaun- 
dice"). The excess of hemoglobin, which cannot be disposed of by the 
liver, may be excreted in the urine (hemoglobinuria). Sometimes 
hemoglobin infarcts are met with in the renal tubules; and thrombosis 
of the renal or other blood-vessels is occasionally observed. Acute 
nephritis is a rare result. 

Pathological Physiology. — Hemocytolysis leads to more or less 
pronounced disturbance of the internal or tissue respiration, as the al- 
tered hemoglobin is incapable of carrying oxygen. Dyspnea and various 
nervous symptoms are the result. The liberation of cellular con- 
stituents (from destruction of the red and white corpuscles) occasions 
increased coagulability of the blood and the formation of thrombi in 
arterioles and capillaries. Fever and other general symptoms may be 
due to the same cause (ferment intoxication). 

POLYCYTHEMIA 

Polycythemia, or erythrocytosis, is a condition in which the number 
of red corpuscles in a given bulk of blood is increased. It is met with 
in a variety of conditions, including certain cardiac diseases with slow 
failure of compensation, and especially in congenital cyanosis; in car- 
bon-monoxid poisoning and other forms of cyanosis; in residents of high 
altitudes; in the newborn; and in cases of cholera or other diseases in 
which liquid discharges cause inspissation of the blood. The explana- 
tion of the increased number of corpuscles in some of these conditions 
has occasioned considerable controversy. It is manifestly possible 
that erythrocytosis may be relative when the number of corpuscles is not 
actually increased, but their proportion in a given bulk of blood en- 
hanced by diminution in the amount of plasma; or actual when there is 
an increase in the total number of red cells in the body. It does not 
seem probable that relative erythrocytosis could have more than a 
brief duration, as in cases of cholera. It is possible, however, that in 
certain conditions in which the peripheral circulation is stagnant the 
number of corpuscles in a given bulk of blood drawn from the finger or 
ear might be relatively increased, without any actual general erythrocy- 
tosis. The higher count of red corpuscles in the blood of dependent 
parts or in a finger congested by constriction or cold lends some color 
to this view. Recent investigators tend toward the opinion that lasting 
erythrocytosis is an evidence either of stimulation of the bone-marrow, 
as a result of conditions which interfere with oxidation, or of abnormal 



428 



A TEXT-BOOK OF PATHOLOGY 



activity of the spleen. The association of marked splenic enlargement 
in some cases is cited as evidence of the latter view; but convincing proof 
of the relationship is lacking. 

Polycythemia with Chronic Cyanosis and Enlarged Spleen. — A 
clinical entity comprising these symptoms, together with weakness, 
prostration, and vertigo, has recently been recognized. No explanation 
has thus far been given for this condition. In some cases the spleen 
was found to be tuberculous; in others only chronic hyperplasia was 
found. 

Besides the conditions before referred to as causing cyanosis and 
polycythemia, certain pulmonary diseases, such as emphysema and 
chronic poisoning with coal-tar products, such as acetanilid and anti- 
pyrin, must be recalled. In some of these cases the spleen may be 
enlarged and the condition may simulate the one just under considera- 
tion. In the reported cases of chronic cyanosis with polycythemia, 
however, these causes of the polycythemia and cyanosis as well as the 
ones before referred to are wanting. 

LEUKOCYTOSIS 

The term "leukocytosis" is given to a more or less transient, but ex- 
ceptionally chronic, increase in the number of leukocytes, under the 
stimulus of a foreign agent, bacterial or toxic, or of diseases outside 
the blood-making organs. The terms "polymorphonuclear leuko- 
cytosis," "lymphemia," "eosinophilia," and "myelocythemia'^ are used 
to designate increase of the polymorphonuclear leukocytes, lympho- 
cytes, eosinophiles, and myeloid elements respectively. 

Etiology. — The causes of leukocytosis are varied. An excessive num- 
ber of leukoctyes in comparison with the figures found in adults is gen- 
erally observed as a normal condition in the newborn, the number of 
corpuscles remaining in slight excess during the first year of life. "Phys- 
iologic leukocytosis" also occurs in many cases of pregnancy; and is 
quite constant during the period of digestion in healthy persons, protein 
food being more striking in the effect than a farinaceous or mixed diet. 
In some diseases of the stomach postdigestive leukocytosis seems not 
to occur. 

Inflammatory and Infectious Leukocytosis. — Among the strictly 
pathological forms of leukocytosis the most important are those due 
to inflammations and infections of various kinds. Croupous pneu- 
monia occasions considerable increase of leukocytes in most cases, and 
this is continuous until the final decline of the fever. Suppurations of 
all kinds act in a similar manner. Inflammations of the serous mem- 
branes — peritonitis, pleurisy, meningitis — may be attended by moderate 
or severe leukocytosis. Among the acute infectious fevers there are 
some in which leukocytosis occurs and others in which this is wanting, 
and this fact often proves valuable to the clinician. Among those in 
which the leukocytes do not increase in number are typhoid fever, in- 
fluenza, malaria, and acute miliary tuberculosis. 



DISEASES OF THE BLOOD 



429 



Cachectic leukocytosis occurs in a variety of marantic conditions, 
and toward the end of life in any case of wasting disease there may be a 
great increase in the number of leukocytes. This agonal or terminal 
leukocytosis is either cachectic (toxic) in nature or it may be due to 
terminal infections. 

Malignant tumors frequently cause leukocytosis. 

Hemorrhage may occasion increase in the number of white corpuscles, 
more or less proportioned to the quantity of blood lost. 

Mechanical and Thermal Causes. — Massage and cold baths fre- 
quently cause increase in the number of leukocytes for a time. 

Medicinal leukocytosis, or that due to the introduction of various 
drugs, is probably allied to infectious and cachectic leukocytosis in the 
manner of its production. 

Pathogenesis. — The nature of leukocytosis has been the subject of 
much controversy. The earliest view regarding the pathogenesis of 
leukocytosis was that in some manner excessive production of leuko- 
cytes took place either in the blood or elsewhere. Later some investiga- 
tors claimed that there was evidence that the leukocytes were not de- 
stroyed as rapidly as in health. Still later the presence of chemotactic 
substances, positive or negative, in the blood was regarded as the cause 
of increase or decrease of leukocytes. At present it seems correct to 
interpret leukocytosis as a reaction of the blood-making tissues to 
agents which stimulate them to overactivity. Such influence is most 
frequently manifested in the bone-marrow (which occasions the preva- 
lent type of leukocytosis — polymorphonuclear), but sometimes the 
lymphatic glands are principally affected and lymphemia results. 

Dormant myeloid elements in the spleen or elsewhere may be 
stimulated to activity and may play a considerable part in the de- 
velopment of leukocytosis. This is more likely to be the case in more 
chronic types. 

According to present conceptions, the explanation of leukocytosis on 
the basis of chemotactic effects of circulating toxic agents, the blood- 
making organs being only passive participants, must be abandoned. 

As a reaction on the part of blood-making tissues is the important 
feature in the process, it follows that toxic agents too feeble to excite 
such reaction may fail to produce leukocytosis; and overactive irritants 
may have a paralyzing effect. 

Character of the Blood. — The blood in leukocytosis varies consider- 
ably in character. The number of leukocytes may be only moderately 
increased (10,000 to 20,000) or may be excessive (50,000 to 100,000). 

In the majority of cases of leukocytosis the polymorphonuclear 
elements are in relative as well as actual excess, the mononuclear ele- 
ments being actually increased in number, but relatively deficient 
(Fig. 178). The proportion of polymorphonuclear elements is frequently 
80 to 85 per cent., and sometimes 90 or 95 per cent., instead of 65 to 70 
per cent. In the leukocytoses following hemorrhage, in cachectic leuko- 
cytosis, in septic leukocytoses, and that due to malignant tumors the 
polymorphonuclear cells are usually increased, while in the leukocytosis 



430 



A TEXT-BOOK OF PATHOLOGY 



of the newborn and in some tumors, especially lymphomata, the mono- 
nuclear elements predominate. Lymphemia is occasionally met with in 
infections in which ordinarily polymorphonuclear leukocytosis would 
occur. Some unknown factor, perhaps individual, operates in such 
cases. Lymphemia is also observed in pertussis, syphilis, typhoid fever, 
and scarlatina. Eosinophilia has been observed in a variety of skin 
diseases, in animal parasitism, especially trichinosis, in anaphylaxis, 
asthma, etc. Myelocythemia has been found in various severe infec- 
tions and in cases of metastasis of tumors to the bone-marrow. It is 
often pronounced in the so-called anemia pseudoleukemica infantum. 

Pathological Physiology. — Leukocytosis certainly exercises some 
profound influence upon the system, but the exact nature of this influence 
is unsettled. Those who contend in favor of the phagocytic theory of 
immunity claim, more or less directly, that the increase of leukocytes 
is a protective process, the purpose being the removal and destruction of 
irritants. This view seems to have gained ground with increased 




Fig. 178. — -Septic leukocytosis, showing marked increase of polymorphonuclear leukocytes. 

knowledge of the mechanism of infection. Others believe that leuko- 
cytosis is part of the cellular processes concerned in the production of 
immunizing substances. There is certainly more active destruction of 
leukocytes in leukocytosis than in health, as is evidenced by the increase 
of xanthin bases and uric acid in the urine; and it may be that in this 
destruction protective substances are liberated. 

LEUKOPENIA 

This is a condition in which there is deficiency in the number of 
leukocytes. This is met with in moderate degree in various diseases, 
such as tuberculosis, typhoid fever, some cases of cachexia, inanition, 
splenomegaly, progressive pernicious anemia, etc. The nature of the 
condition is not entirely clear. Some have held that it is due to destruc- 
tion of leukocytes (leukolysis) , while others claim that it is the result 
of altered distribution of the leukocytes. It has been shown by experi- 
menters that the injection of certain micro-organisms or toxic sub- 



DISEASES OF THE BLOOD 



431 



stances may produce, first, a decrease in the number of leukocytes, and 
then an increase. The primary leukopenia is explained by some as the 
result of active destruction of leukocytes, but the conditions of the 
urine do not give evidence of such active destruction, and others have 
shown that the capillaries of the lungs, liver, and other organs are 
overfilled with leukocytes during this stage. The assumption, therefore, 
seemed warranted that leukopenia might result from disturbance in the 
distribution of the leukocytes. 

According to more modern conceptions, however, leukopenia may be 
regarded as a result of unfavorable action upon the blood-making tis- 
sues of toxic agents. 

ANEMIA 

Definition. — This term includes a variety of conditions in which 
the blood is reduced in quality in one constituent or another. The term 
oligocythemia indicates a reduction in the number of red corpuscles, 
while the name oligochromemia indicates a reduction in the coloring- 
matter of the corpuscles. Usually these conditions are associated. 

Classification of Anemias. — It is not as yet possible to offer a 
strictly scientific classification, but for ordinary purposes the old division 
into -primary and secondary anemias may be retained. The term "primary 
anemia" may be given to forms in which the anemia is the striking path- 
ological condition. The older writers used the name to indicate that the 
anemia was an essential disease of the blood itself and dependent upon 
no preceding affection, excepting possibly a disturbance of the hemato- 
poietic organs. The term "secondary anemia," or "symptomatic 
anemia," may be used to designate anemic conditions in which some 
underlying disease that has occasioned the anemia is conspicuous. Ac- 
cording to the classification here offered, all anemias are recognized as 
secondary in the strict sense, but those in which the underlying disease 
is not conspicuous are classified as primary, and those in which the orig- 
inal disease is conspicuous as secondary. Another aspect of the matter, 
within the terms of the definition, is that in the diseases classified as 
primary, the effects of the original condition, whether toxemia, infec- 
tion, or of other sort, are manifested most strikingly in the blood-making 
apparatus. In the secondary anemias such effects are subsidiary in 
importance and relatively inconspicuous. 

THE SECONDARY ANEMIAS 

Etiology. — Various unsanitary conditions may influence the char- 
acter of the blood by the constant disturbance of the organic functions. 
A cause of immediate anemia is hemorrhage. This first leads to reduc- 
tion in the quantity of blood; and later by absorption of liquid from the 
tissues to dilution of the blood, or hydremia. Finally, after a variable 
period, the character of the blood is restored by regeneration of cor- 
puscles and of coloring-matter. Parasites of various sorts may lead 
to anemia. Among the more important are the intestinal worms, 



432 



A TEXT-BOOK OF PATHOLOGY 



Uncinaria duodenalis, Dibothriocephalus lotus, and Anguillula intes- 
tinalis. The mode of action of these is not entirely clear. Some have 
held that they cause anemia by loss of blood through the intestine, and 
this is probably true in the case of Anguillula and Uncinaria, but marked 
anemia may occur from the presence of Bothriocephalus, which is not 
a blood-sucker and does not occasion hemorrhage. An explanation 
worthy of consideration in these cases is that the parasites generate 
poisons either in their ordinary life or by their death and decomposi- 
tion, and that these poisons are the cause of the anemia. Recent in- 
vestigations seem to indicate that certain lipoids are the direct hemolytic 
cause of the anemia in cases of bothriocephalus invasion. Other in- 
testinal parasites may occasion more or less anemia directly or indi- 
rectly. The parasites occurring in the blood itself, notably the malarial 
organism, may cause extreme anemia. Infectious diseases, especially 
streptococcus infections, frequently lead to impoverishment of the 
blood. In the acute febrile diseases, such as typhoid fever, rheumatism, 
and pneumonia, the anemia may not be conspicuous during the progress 
of the disease, but becomes apparent after the fever has subsided. 
This may be explained by the assumption that increased respiration 
and sweating cause inspissation of the blood and relative increase 
in the number of red corpuscles during the existence of fever, so that 
the anemia is unnoticed. In chronic infections, such as syphilis and 
tuberculosis, marked anemia may occur. Among the poisons capable of 
producing anemia are lead, arsenic, phosphorus, and other metallic sub- 
stances, and experimentally pyrogallol, nitrobenzol, pyrodin, and various 
coal-tar products have been used to produce anemia. The anemias of 
various infectious diseases are undoubtedly toxic in character, and very 
probably those occurring in gastro-intestinal and nutritional diseases 
are similarly the result of the action of poisons generated within the 
body. Organic diseases and new grotoths of various sorts may occasion 
anemia by the general disturbance of health, by toxic products gener- 
ated in the course of disease, or by hemorrhage. 

Pathological Anatomy. — The condition of the blood in secondary 
anemias varies with the duration and grade of the anemia. In moderate 
cases the number of red corpuscles decreases slightly (4,000,000 to 
3,000,000), and the hemoglobin is correspondingly reduced, though 
usually somewhat more strikingly than the corpuscles. The fresh blood 
may show no visible changes under the microscope, and even in stained 
preparations the appearance may be normal. More marked anemia is 
distinguished by greater reduction, the number of corpuscles sinking to 
2,500,000 or 2,000,000 per cubic millimeter in extreme cases. Examina- 
tion of the fresh blood shows pallor of the corpuscles and various irregu- 
larities in size (microcytes and megalocytes) and shape (poikilocytes). 
Nucleated red corpuscles may be present in small numbers, normo- 
blasts predominating. The stained blood may disclose degeneration of 
the corpuscles by the presence of polychromatophilic forms. The 
leukocytes do not play an essential part in this form of anemia. Their 
number may be normal or reduced ; in other cases leukocytosis is present. 



DISEASES OF THE BLOOD 



433 



The relative proportions of the different forms is usually about normal. 
Myelocytes are occasionally present. 

Associated changes in various organs may be met with. Among these 
are parenchymatous and fatty degeneration of the heart, kidneys, and 
liver. These conditions have often been ascribed to reduced oxidation, 
which was supposed to be due to poverty in hemoglobin. Physiological 
studies, however, do not establish the existence of a reduction in the 
respiratory exchange of gases. It is likely that toxic conditions of the 
blood occur in anemia, and that the poisons act directly upon the 
affected organs. 

Pathological Physiology.— The process of oxidation is of particular 
interest in anemia, and, as has been stated, recent investigations show 
that the consumption of oxygen and elimination of carbon dioxid are 
normal. To accomplish this result more active circulation and greater 
energy of the tissues are required. Partly in consequence of the latter, 
diseases of the organs named in the last paragraph result; and at the 
same time some of the characteristic symptoms (palpitations, dyspnea) 
are produced. In severe secondary anemias increased tissue-waste oc- 
curs, and nitrogen is discharged in excess of that digested. 

THE PRIMARY ANEMIAS 

The principal conditions included under this title are chlorosis, 
progressive pernicious anemia, leukemia, and Hodgkin's disease. The 
modern tendency is to discuss the last two apart from anemias; but not 
only established custom, but the involvement of blood-making organs 
and the occurrence of actual anemia in these diseases justify the classi- 
fication adhered to. The term simple primary anemia is sometimes used 
to designate a form of anemia without distinct cause, and characterized 
by moderate oligocythemia. There are, it is true, occasional cases of 
moderate anemia in which no definite precedent disease can be discov- 
ered; but these are exceptional cases, and are to be considered as second- 
ary anemias in which the underlying disease is latent. Cases of this 
sort do not conform to a definite type, and cannot, therefore, be con- 
sidered as illustrating a special form of anemia. Another term fre- 
quently used is splenic anemia. This is even less satisfactorily defined. 
Splenic enlargement may occur in any of the primary anemias, and may 
in some cases be excessive. Moreover, some of the distinctly secondary 
anemias (as those of rickets, syphilis, and malaria) are very often 
attended with splenic enlargement. There is a group of conditions 
properly included under the title splenomegaly in which more or less 
anemia may occur, but this title rather than splenic anemia is prefer- 
able. 

CHLOROSIS 

Definition. — Chlorosis is a primary anemia due to retarded hemo- 
genesis, characterized by a peculiar pallor and marked reduction in the 
percentage of hemoglobin, and occurring almost exclusively in young 
girls and women. 

28 



434 



A TEXT-BOOK OF PATHOLOGY 



Etiology. — Chlorosis is most frequent at the time of beginning men- 
struation and during the years immediately following this. A form of 
late chlorosis has been described in women above thirty years of age 
and at the menopause; but the nature of this is doubtful. Chlorosis in the 
male is still more doubtful, though a few cases have been described by 
competent observers. Hereditary tendencies are of etiological impor- 
tance. The disease occurs more frequently in families in which tuberculo- 
sis is common than in those not so affected. Constitutional predispo- 
sition is also an important factor, poorly developed girls, and particularly 
those of delicate mould, being especially liable to the disease. Virchow 
found hypoplasia of the heart and great vessels, and Rokitansky the 
same condition in the generative organs, and pathologists have been 
inclined to regard these as important factors in the development of the 
disease. 

Various exciting causes have been considered as of more or less 
importance. Emotional excitement was regarded as a prime cause by 
ancient authorities, and in consequence such terms as icterus seu febris 
amantium were applied. Home-sickness, grief, etc., are causes of 
moment. Intestinal auto-intoxication has been regarded as the essen- 
tial factor by many, but physiological chemists fail to find evidences of 
the existence of such intoxication. Menstrual disturbances are im- 
portant as symptoms, and have often been regarded as causes. The 
hypoplasia of the genital organs adds some probability to this view, 
but more definite evidence is wanting. Von Noorden strongly ad- 
vocates a theory that chlorosis is due to a failure of some internal secre- 
tion of the ovaries. 

At the present time it seems most likely that chlorosis is due to 
faulty development, and especially to a want of proper hemogenetic 
power. 

Pathological Anatomy. — The hypoplasia of the vascular and gener- 
ative systems has been referred to. These are primary lesions, and 
possibly causal. Various secondary diseases may be encountered, as in 
other anemias. Among these, myocardiac degeneration and dilatation 
are most important, though they do not attain high grades of severity. 
The spleen is frequently a little enlarged. Peculiar yellowish or greenish 
pigmentation of the skin is a striking feature. The pigment is doubtless 
altered hemoglobin, but its exact nature is unknown. 

The blood is paler than normal and watery. The specific gravity 
decreases progressively, and the solid matter is deficient. Increased 
coagulability is sometimes observed. The number of red corpuscles 
may be normal, even in well-developed cases, but the proportion of 
hemoglobin sinks progressively. In prolonged cases the corpuscles 
become reduced in number, but the deficiency of hemoglobin continues 
to be excessive. Severe cases of chlorosis frequently show 3,000,000 or 
2,000,000 red corpuscles per cubic millimeter and 30 to 20 per cent, of 
hemoglobin. The red corpuscles may be little altered in appearance 
in the early stages; later, great pallor of the cells, and irregularities in 
size and shape are frequent, nucleated red corpuscles (especially normo- 



PLATE 3 




Pernicious anemia. (Drawing made under the direction of Dr. C. Y. White.) 




DISEASES OF THE BLOOD 



435 



blasts) make their appearance. The latter sometimes occur in great 
numbers in crops (blood crises). The leukocytes are usually normal 
in number and kind; but in some cases myelocytes have been met 
with. 

During the process of recovery from chlorosis the red corpuscles 
increase in number before any change occurs in the percentage of hemo- 
globin. 

Pathological Physiology.— Chlorosis resembles the secondary ane- 
mias in most particulars, as far as its influence on the general health is 
concerned. Some of the symptoms (cardiac and menstrual) are doubt- 
less due to primary abnormalities of structure. The preservation of the 
subcutaneous fat despite advancing anemia is a striking feature. It 
is explained by von Noorden on the assumption that the quiet and 
warmth which chlorotics find necessary to their comfort lead to accu- 
mulation of fat. Decreased oxidation is certainly not the cause. 

PROGRESSIVE PERNICIOUS ANEMIA 

Definition. — Progressive pernicious anemia is a form of hemolytic 
anemia characterized by certain hematologic features significant of 
pathological activity of the bone-marrow. It is probably always fatal, 
though a few instances of recovery have been reported by competent 
authorities. An exact definition and a positive clinical differentiation 
from certain other conditions are not possible. 

Etiology and Pathogenesis. — The disease was first described by 
Addison as a wholly causeless anemia, that is, an anemia independent 
of preceding disease of any sort. Subsequent investigation seemed to 
show that it might be secondary to other diseases. Thus intense 
anemias were found during pregnancy and lactation, in certain gastro- 
intestinal affections, including atrophy of the gastric and intestinal 
mucosa, ulcerations and carcinoma, and in cases of intestinal parasit- 
ism (uncinaria, bothriocephalus) . A rigid scrutiny of such cases dis- 
closes the fact that these are usually instances of intense secondary 
anemia, though the resemblance to true pernicious anemia may be 
puzzlingly close. In the cases in which true pernicious anemia must be 
admitted the relation may be merely a coincidence. Considerable 
evidence has, however, accumulated to show that gastro-intestinal 
infections and toxemias may be the underlying cause of the disease. 
First, it was shown that pernicious anemia is essentially a hemolytic 
anemia from the facts that the blood-picture is in many respects that 
of direct experimental hemolytic anemias, that the pigmentation of the 
liver and spleen indicate hemolysis, and the urine and feces give evidence 
of excessive liberation of blood-pigment. Second, it was noted that the 
distribution of pigment in the liver and spleen strongly suggested hemol- 
ysis in the area of the portal circulation; and third, the frequent asso- 
ciation of oral infection (glossitis, ulcers in the mouth, on the gums, 
etc.) or gastro-intestinal disease further strengthened this view. The 
discovery of hemolytic substances in the bodies of bothriocephalus taken 



436 



A TEXT-BOOK OF PATHOLOGY 



in conjunction with the anemia occasioned by this parasite was another 
factor in the evidence. 

There is some ground for believing that some sort of primary vul- 
nerability of the bone-marrow may be of importance; but it is much 
more probable that the marrow is affected by toxic agents derived from 
outside sources than that there is a primary disease of the marrow. 

Among clinical causes: age (usually after adult years have been 
reached); sex (more often females); nervous shocks, privation, and 
insanitary surroundings have been noted. Malaria, syphilis, tubercu- 
losis, and other infections, as well as repeated hemorrhages, have been 
regarded as causes. In connection with all of these it must be remem- 
bered that the differentiation of intense secondary anemia from per- 
nicious anemia is often very difficult. 

Pathological Anatomy. — Various secondary changes are met with, 
those in the blood-making organs being most important. The bone- 
marrow of the long bones is red and softened and often quite hemor- 
rhagic (for details, see Bone-marrow). This change was formerly re- 
garded as a primary and causal one. At the present time it is looked upon 
as secondary and reactive to a toxemia and, in part, to the hemolytic 
anemia itself. In part, at least, it represents the effort of the bone- 
marrow to compensate for the active blood destruction. The spleen 
is sometimes enlarged, and may be considerably so. (Pigmentation of 
the spleen will be referred to below.) 

The liver, kidneys, and especially the heart suffer degenerative 
changes (fatty) in severe cases. Similar alterations in the blood-vessels 
may cause punctate hemorrhages (especially in the retina), or larger 
hemorrhages in various situations. The lesions of the gastro-intestinal 
tract have been referred to. Some of them are doubtless secondary to 
the anemia; others may be primary. 

Degenerations of the posterior and lateral columns of the spinal 
cord are frequent. They seem to be due to a toxic agent rather than to 
hemorrhages. 

Pigmentation of the liver, spleen, kidneys, and other organs is a 
significant condition in evidence of the active hemolysis supposed 
to occur in this disease. The pigmentation of the liver is most impor- 
tant, and seems to be characteristic. It occurs in the hepatic cells at the 
periphery of the lobules and in the endothelial cells of the lymphatic 
channels and capillaries in the same situation. The pigment is iron- 
containing, and may be well demonstrated by applying the iron reac- 
tions (sulphid of ammonium; hydrochloric acid and ferrocyanid of 
potassium — forming Prussian blue). 

The Blood. — The color of the blood is often strikingly pale; though 
it may be dark in spite of marked anemia. In some strikingly hemol- 
ytic cases the blood-plasma may be deeply tinged with hemoglobin or 
with bile-pigment. The specific gravity is reduced. The marked feat- 
ures of the disease are pronounced oligocythemia, marked changes in the 
character of the red cells, and a color-index somewhat above normal, 
which contrasts with the low color-index of severe secondary anemias. 



DISEASES OF THE BLOOD 



437 



The oligocythemia progresses rapidly, and in ordinary cases the number 
of red corpuscles sinks to 1,000,000 or less per cubic millimeter; at the 
same time changes in size (microcytes and megalocytes) and in shape 
(poikilocytes) make their appearance, and reach grades rarely attained 
in other diseases (Fig. 179). An important feature is the number of 
macrocytes. A general survey of the microscopical field at once indicates 
that the average size of the corpuscles is evidently increased. Nu- 
cleated red corpuscles are always present in some numbers and are 
usually abundant (Fig. 179). The larger and polychromatophilic forms 
(megaloblasts), as a rule, predominate; but in some cases the smaller 
forms are more abundant. Karyokinetic figures may be found in the 
nuclei. Polychromatophilia and basic granulation are generally pro- 
nounced. The leukocytes may be decreased or normal in number; in 
the late stages leukocytosis is not uncommon, and it may become quite 



Fig. 179. — Blood in pernicious anemia, showing irregularity in the size and shape of 
the red corpuscles; one nucleated red corpuscle (megaloblast) and two lymphocytes; stained 
with Ehrlich's triple mixture. 



marked. The larger mononuclear leukocytes are usually more abun- 
dant than in health, and myelocytes often occur in considerable numbers. 
In the terminal leukocytosis of pernicious anemia the lymphocytes often 
predominate. 



Occasional cases of severe anemia running a rapid course to a fatal 
termination have been reported, in which the bone-marrow has shown 
a high grade of hypoplasia or even total aplasia. In these cases the 
blood gives evidence (marked reduction in the number of red cells, low 
color-index, great reduction of the proportion of polymorphonuclear 
cells, relative and actual increase of lymphocytes, absence of myelo- 
cytes and very few nucleated red cells) of the inactivity or aplasia of the 
marrow. These cases seem classifiable as types of progressive pernicious 
anemia in which the response of the bone-marrow to the demand for 
hemogenesis is nearly or quite wanting. Possibly the toxic agent may 
be directly destructive to the bone-marrow, as it is to the blood. 

The bone-marrow is yellow or white, and on microscopical section 
the specific marrow cells may be wholly wanting. 




APLASTIC ANEMIA 



438 



A TEXT-BOOK OF PATHOLOGY 



HEMOLYTIC ICTERO-ANEMIA 

In recent years several clinical types of hemolytic anemia with 
jaundice have been described. These may properly be discussed here 
because of the close relationship in pathogenesis and the difficulty 
in fully differentiating some of these conditions, either clinically or 
pathologically, from genuine pernicious anemia. The evidences of 
hemolysis are more striking in these diseases, while the indications 
of bone-marrow reaction are less marked, but border-line cases merge 
gradually into the picture of pernicious anemia. 

A congenital and an acquired form of hemolytic ictero-anemia have 
been described. In each there is more or less pronounced anemia, 
jaundice, and splenic enlargement. The congenital form often affects 
several members of a family, is comparatively mild, and may continue 
for years without grave disturbance of health. Splenic enlargement 
is marked. In the acquired form the anemia and jaundice are more 
marked and splenic enlargement usually less so. The prognosis is more 
grave. In both, the evidences of hemolysis (jaundice, without acholic 
stools, urobilinuria, hemorrhagic tendencies) are pronounced. The 
red corpuscles show decided fragility, being hemolyzed in much more 
concentrated salt solutions than are normal red corpuscles. 

LEUKEMIA 

Definition. — Leukemia is a hyperplastic disease of the hemogenic 
organs accompanied by increase in the number of leukocytes in the 
circulating blood, and by the presence also of cell types not found 
normally outside the blood-making tissues. 

Etiology. — The actual cause of leukemia, as well as the essential 
nature of the disease, remain obscure. Various diseases (malaria, syphilis, 
rickets, etc.) have been regarded as predisposing causes. The same is 
true of pregnancy, lactation, traumatism, exposure,* and other in- 
fluences. To some, heredity has seemed to be an important element. 

Infection has been suspected as the direct cause of leukemia by many 
observers, and various forms of bacteria have been discovered in the 
blood and tissues. There are certainly some very striking facts in favor 
of an infectious nature, the most important being the apparent con- 
tagiousness in a few cases. The various micro-organisms need not be 
enumerated, as none of them has been proved to be pathogenic. Bodies 
resembling protozoa have been found in the blood and in the organs 
(lymphatic glands), but the nature and significance of these are un- 
certain. 

Pathological Anatomy. — It is impossible to classify leukemia with 
certainty, but the evidence at present seems to justify the belief that it 
is closely related to neoplastic processes. Reference to this aspect of the 
matter will be found in the sections on Lymphatic Glands and Bone- 
marrow. 

In a certain sense the lesions of leukemia might be classed as hyper- 



DISEASES OF THE BLOOD 



439 



trophy or hyperplasia of the hemogenic tissues ; but there is evidence of a 
progressive process that goes beyond the limits of ordinary hypertro- 
phies. Enlargement of the spleen or of the lymphatic glands is the 
conspicuous pathological feature. The secondary lesions in organs that 
have ceased to be active hemogenic structures (spleen, liver, and peri- 
vascular tissues elsewhere) appear to be metaplastic, in the sense that 
the endothelia may reassume a latent capacity and as in fetal life initiate 
new series of blood-making cells. This process rather than metastasis or 
mere deposition accounts for the foci of myeloid or lymphadenoid tissue 
found in practically all parts of the body. Two types of leukemia may 
be distinguished : the myeloid or myeloic and the lymphatic. The former 
originates in the bone-marrow, and is characterized by hyperplasia of the 
myelocytic series of cells. Not only myelocytes, but their predecessors, 
myeloblasts and various intermediary stages representing undeveloped 
myelocytes, may make up the bulk of the tissue. The erythroblastic 
cells are crowded out, though not invariably, and exceptionally may be 
conspicuous. In certain cases, especially in very acute forms, myelo- 
blastic cells difficult to distinguish from cells of the lymphocytic series 
may be conspicuous both in the lesions of the bone-marrow and 
other organs and in the blood. Many if not most of the cases of 
so-called acute lymphatic leukemia 
belong in this group. Lymphatic 
leukemia originates in the lymphatic 
glands or other lymphadenoid tissues, 
and consists essentially in an active 
proliferation of lymphocytes. The 
bone-marrow, spleen, and other organs 
may be secondarily involved. The 
contention that all forms of leukemia 
originate in the bone-marrow, which 
was at one time commonly believed, 
was largely based upon the discovery 
that sometimes in so-called acute 
lymphatic leukemia the bone-marrow 
was found affected and not the lymph- 
atic glands. In the light of present 
knowledge these cases were probably 
instances of myeloblastic leukemia. 

Occasionally the primary disease is in the lymphadenoid tissues of 
the gastro-intestinal tract. Primary dermal leukemia has been de- 
scribed (lymphodermia perniciosa), but is not satisfactorily established. 

Among the secondary lesions of leukemia are invasions of the liver, 
kidneys, lungs, heart, and other tissues. The organs show areas of light 
color, or a streaked or mottled appearance, due to masses of myelo- 
cytic or lymphoid cells (Fig. 180). Secondary degenerations of the 
heart, liver, and kidneys may result from the deposits, or from the im- 
poverished state of the blood and the presence of toxic substances. 
Scleroses of the spinal cord may be met with, as in pernicious anemia. 




Fig. 180. — Lymphoid infiltrations 
between the renal tubules, from a case 
of leukemia. 



440 



A TEXT-BOOK OF PATHOLOGY 



The blood is often light in color and may be quite milky in appear- 
ance. The specific gravity is lowered. Coagulation is slow; this has 
been attributed to the presence of albumoses in the blood. 

The conspicuous feature in the blood is the increased number of 
leukocytes. In moderate cases there are from 100,000 to 300,000 white 
corpuscles per cubic millimeter. In severe cases the number is much 
greater; while in mild or beginning cases, or in cases under active treat- 
ment, the number may for a time be normal or subnormal. Rapid 
fluctuations in number are very common. 

Leukemia is usually a chronic disease. The blood-picture indicates 
the type of the lesions, and we may thus recognize a myeloid or 
lymphatic form. 

Myeloid Type. — Enlargement of the spleen is the conspicuous clin- 
ical feature. The blood presents a great excess of white corpuscles 
and more or less decided poverty in red cells. The proportion of 
white to red corpuscles is often 1 : 3, 1 : 2, or even 1: 1. The larger 
mononuclear leukocytes (including normal mononuclear and transi- 
tional elements and myelocytes) predominate over the lymphocytes 
and polymorphonuclear elements (see Fig. 175). The latter two forms, 
however, are actually increased. Myelocytes are usually found in 
great numbers, and evidence the myeloid nature of the disease. Not 
only the typical neutrophilic myelocyte, but more or less abundant 
eosinophilic and basophilic forms and some without granules or with a 
mixture of basophile and neutrophile granules may be found. Cells 
corresponding to the myeloblasts may also be found, sometimes abun- 
dantly, especially in acute cases. There is usually an actual increase in 
the number of eosinophile elements, but the percentage proportion is 
rarely increased. Basophilic leukocytes (mast-cells) are present in 
numbers greatly in excess of those found in health. Karyokinetic leuko- 
cytes are found in small numbers. The red corpuscles present the usual 
features of anemic blood, and nucleated forms, especially normoblasts, 
may be abundant. The blood-picture is an extremely variegated one, 
and the predominence of large cells is the feature that stands out most 
prominently. 

A peculiar constituent of the blood are the Charcot-Neumann crys- 
tals. These are polyhedral, needle-shaped crystals of uncertain com- 
position, met with in the blood after death or some time after removal 
from the body, and exceptionally in the fresh blood. They were first 
detected in the bone-marrow. 

Lymphatic Type. — Enlargement of lymphatic glands is the most 
conspicuous clinical feature. The leukocytes are usually less abundant 
than in the myeloid type. The lymphocytes predominate very greatly, 
but actual excess of large mononuclear forms and polymorphonuclear 
leukocytes is observed. Contrasted with myeloid leukemia the striking 
feature is the abundance of small cells — lymphocytes. The larger 
lymphoblasts are rarely conspicuous except perhaps in certain acute 
cases. Myelocytes occur in small numbers; exceptionally in consider- 



•Jo •**°{3fc 

-oft 




u : 




- 




Acute leukemia. (Drawing made under the direction of Dr. C. Y. White.) 




a 



O ^ QOQ 



o o 

z ~ #O w O 

o °©, 



DISEASES OF THE BLOOD 



441 



able proportion. The number of red corpuscles is decreased and nucle- 
ated red cells may be present. 

Acute Leukemia. — A separate description of acute leukemia is de- 
sirable, because in its clinical manifestations there are striking differences 
from those seen in chronic leukemia and because it is difficult to deter- 
mine whether a given case is myeloid or lymphatic. In the rapid 
progress of the disease cells of great immaturity are cast into the circu- 
lation and opinions vary as to their nature. Some hold that these are 
lymphoblastic; others, that they are myeloblasts. Upon the whole, the 
latter view seems to be more tenable. 

Acute leukemia seems, in some respects, a distinct type of the dis- 
ease, and the symptoms are strongly suggestive of an infectious condi- 
tion. The duration is usually from a few weeks to a few months after 
the first symptoms are noted. Gastro-intestinal lesions (ulcers in the 
mouth, stomach, and intestines) and hemorrhagic manifestations 
(purpura) are frequent. Moderate enlargement of the lymphatic 
tissues and infiltrations of the organs are discovered, and parenchy- 
matous changes in the organs are constantly present. 

The blood shows a varied picture. The total number of leukocytes 
may vary from a very moderate increase above the normal to several 
hundred thousands per cubic millimeter. Mononuclear elements are 
conspicuous, the predominating cell being one that resembles lympho- 
cytes or lymphoblasts, and also the smaller myeloblasts. The nuclei 
are large, round, or horseshoe shaped, and stain faintly; the protoplasm 
forms a somewhat narrow rim around the nucleus. The polymorpho- 
nuclear cells and eosinophiles may be actually, but not relatively, in- 
creased in number; myelocytes are occasionally present. Considerable 
reduction in the number of red corpuscles is a usual feature of acute 
leukemia. Nucleated red corpuscles (especially normoblasts) are gener- 
ally present. 

HODGKIN'S DISEASE 

This disease presents a certain superficial resemblance to leukemia 
in the enlargement of the lymphatic glands and sometimes of the spleen, 
and to a less extent in the histology of the lesions. As the differentia- 
tion has become more definite the old term pseudoleukemia has been 
generally abandoned. 

Hodgkin's disease does not present an increase in the number of 
leukocytes in the blood, or, at most, a very moderate increase. There is 
a moderate but progressive anemia, with occasionally decided eosino- 
philia. In certain cases the polymorphonuclear elements are relatively 
excessive. The lymphatic glands enlarge more quickly than in leukemia, 
and the spleen and marrow are less frequently involved. (See Lymph- 
atic Glands.) 

Pseudoleukemia Infantum 

Under this name von Jaksch described a form of leukocytosis, with 
enlargement of the spleen and liver, occurring in children. There is rapid 



442 



A TEXT-BOOK OF PATHOLOGY 



and excessive oligocythemia, and the leukocytosis is pronounced. Leu- 
kocytes of all types are present, and give to the blood a curiously 
variegated appearance. There is no striking difference, however, from 
the characters of the blood met with in other cases of leukocytosis in 
infancy. Rickets and congenital syphilis seem to be closely related to 
this form of disease. 

The enlargement of the spleen and liver is not of the nature of that 
seen in leukemia, but is simply a chronic hyperplastic condition. 

FOREIGN BODIES AND PARASITES 

Foreign Bodies in Blood. — Various kinds of particles may gain 
access to the blood-current and may be carried to peripheral parts of 
the circulation. In anthracosis a lymphatic gland may attach itself 
and, after softening, rupture into a vein. The particles of carbon are 
thus distributed in the blood. Small portions of tumors, of the heart- 
valves, calcareous particles from atheromatous plates, and portions of 
thrombi are frequently transported by the blood. Charcot crystals 
are met with in leukemia, and pigment-matter, due to disintegration 
of the blood itself, is seen in malaria. 

Parasites in the Blood. — Among the animal parasites are the mala- 
rial plasmodium, which occurs within the red corpuscles or free in the 
plasma; the Schistosomum haematobium, which occupies the portal vein; 
the embryos of the Filaria bancrofti, and the trypanosomes. (These are 
more fully described in the section on Parasites.) Portions of hydatid 
cysts or of cysticerci and trichinae are occasionally conveyed in the 
circulation. 

Vegetable Parasites. — Mould-fungi sometimes gain entrance into 
the circulation and lead to serious embolism, as does also the Streyto- 
thrix actinomyces. Of the pathogenic bacteria, the spirochete of relaps- 
ing fever and the bacillus of anthrax are most abundant in the blood. 
Other micro-organisms are more difficult of demonstration, though 
many kinds of micro-organisms have been demonstrated morpho- 
logically and in culture. 



CHAPTER II 



DISEASES OF THE LYMPHATIC TISSUES 
The Spleen 

Anatomical Considerations. — The spleen is practically a com- 
plicated lymphatic gland with close relations to the circulation. It 
is enclosed in a fibrous capsule, from which trabecular enter into the 
substance of the organ and give off subdivisions that unite and form a 
framework, in the meshes of which lymphoid tissue is embedded. The 
splenic artery enters at the hilum and subdivides into numerous branches 
which traverse the trabecular. Side branches are given off from the 
trabecular arterioles; these penetrate the splenic pulp and are surrounded 
by denser aggregations of lymph-cells, which are visible to the naked eye 
as the Malpighian bodies. All of the terminal arteries discharge their 
blood directly into the spaces of the splenic pulp, from which it is 
re-collected into the veins. The spaces contain, in addition to lymphoid 
cells and red blood-corpuscles, larger cells, endothelial in type, often 
containing pigment granules or even blood-corpuscles. 

The weight of the spleen in the adult varies from 140 to 200 gm. 

The splenic function remains in doubt. It seems to have some con- 
nection with the process of manufacture of leukocytes, and is one of the 
sources of red blood-corpuscles in early life. It may also be the place 
of destruction of red corpuscles, and in cases of general hemolysis, or 
blood-destruction, the blood-pigment and fragmented corpuscles are 
especially arrested in this organ. It has something to do with the iron 
chemistry of the body. The muscular tissue of the capsule contracts 
and expands, assisting thus in the propulsion of blood and lymph. 

Pathological Physiology. — The relations of diseases of the spleen 
to the general health are still obscure. It has been held by some pathol- 
ogists that this organ plays an important part in the process of im- 
munization or combating infectious diseases. The fact that bacteria 
and foreign bodies circulating in the blood are arrested to a large extent 
in the spleen warrants the suspicion that this organ is important in dis- 
posing of irritants, and thus preventing their gaining access to more 
vital parts. Experimenters, however, have found no uniform increase 
of susceptibility to micro-organismal inoculation on the part of splenec- 
tornized animals. For the present, therefore, we can only suspect that 
removal or disease of the spleen renders individuals more vulnerable to 
infections. 

The effect of removal of the spleen in human beings is surprisingly 
slight. A certain amount of anemia and general deterioration of health 
follow the operation, but seem to be the result of the operation -per se, 

443 



444 



A TEXT-BOOK OF PATHOLOGY 



rather than of removal of the organ. Subsequently, complete health 
is regained. Some compensatory (?) enlargement of the lymphatic 
glands has been observed after splenectomy. 

ABNORMAL DEVELOPMENT AND SITUATION 

Complete absence of the spleen has sometimes been noted in children 
that lived for several years. More commonly slighter defects, such as 
unusual smallness or excessive lobulation, occur. Very often small 
accessory spleens, the size of a pea or a marble, are found, occurring 
chiefly in the abdominal cavity, but also found elsewhere. 

Movable Spleen. — -The organ may be quite movable, either as a 
congenital condition or as the result of enlargement and resulting 
traction upon its attachments. Downward displacement and mova- 
bility are frequently found in cases of splanchnoptosis. Twisting of the 
pedicle of a movable spleen may lead to strangulation of the circulation 
and consequent necrosis. 

CIRCULATORY DISTURBANCES 

Anemia may occur in cases of general anemia resulting from hemor- 
rhage or inanition. The spleen presents a contracted appearance, the 
capsule being wrinkled, and on section the substance is found to be 
lighter in color and the fibrous stroma is more prominent than normal. 

Hyperemia may be active or passive. Active hyperemia is a physio- 
logic condition during digestion, when the spleen increases somewhat in 
size. Intense congestion occurs in a number of diseases, but so com- 
monly passes into inflammation that it will be described under that 
heading. Passive congestion is most marked in cases of cirrhosis of the 
liver, but also occurs in association with hyperemia of other organs as 
the result of cardiac failure, of emphysema, or of other diseases obstruct- 
ing the larger venous channels. The spleen is greatly enlarged and of a 
dark-red color, and the capsule is often tensely distended; the Mal- 
pighian bodies are less distinct than normally. After long continuation 
of the process hyperplasia of the trabecular and the fibrous stroma 
generally takes place. The spleen may be greatly enlarged and very 
dense at this stage. Subsequently contraction of the newly formed 
fibrous tissue may lead to atrophy of the proper splenic substance and 
increased induration of the organ (cyanotic induration). Considerable 
pigmentation is found in such cases from the destruction of the stag- 
nated blood (see p. 448). H. A. Christian, in a study of the spleen in 
cases of chronic passive congestion and cirrhosis of the liver, found no 
change of any kind in the Malpighian bodies of the spleen. The pulp 
was relatively poor in cells and the blood sinuses generally dilated. 
There was also, as a rule, a definite layer of low cuboidal endotheial 
cells lining the sinuses. In a majority of the cases there was increase 
of the connective-tissue framework. In the 10 cases with no increase 
in connective tissue, the spleen felt almost equally firm, showing that 



DISEASES OF THE LYMPHATIC TISSUES 



445 



the firmness was due to vascular distention. The same factor probably 
enters into the production of firmness in all of the cases. Proliferation 
of the reticular tissue of the pulp with little or no change in the white 
fibrous and elastic tissue of the organ, constituted the main connective 
tissue change. An increase of connective tissue around the small 
splenic arteries and within the Malpighian bodies was sometimes seen. 

Hemorrhages in the spleen may be the result of traumatism, when 
large hematomata may form, especially just beneath the capsule. 
Small areas of hemorrhage are not infrequent in intense infections with 
splenitis, but it is difficult to draw a line between hemorrhage and the 
overfilling of the spaces by congestion, since the blood under normal 
conditions enters directly into the splenic pulp. 

Embolism of the splenic artery is very common in cases of endo- 
carditis or thrombosis in the left heart or aorta. As the spleen contains 
abundant "terminal arteries," infarction is the common result. The 
area may remain light colored, constituting an anemic infarct; or it 
may become overfilled with blood, when hemorrhagic infarction results. 
In either case there is a wedge-shaped lesion, with the base toward the 
surface of the organ and the apex within, harder than the surrounding 
tissue and usually somewhat elevated. The swelling and elevation 
in the case of anemic infarction are partly due to a zone of hyperemia 
which usually surrounds it. Complete resolution may occur, but more 
commonly the area involved undergoes coagulation necrosis and soften- 
ing, and as absorption takes place fibrous overgrowth gives rise to the 
formation of a scar. There may be numerous infarcts of small size or a 
single large one sometimes occupying as much as half of the organ. 
(Septic infarction and its results are discussed under Abscess of the 
Spleen.) 

Thrombosis of the splenic vein may occur in association with throm- 
bosis of the portal vein. It causes intense passive hyperemia of the 
spleen. Occasionally calcification of thrombi gives rise to the forma- 
tion of splenic stones. 

INFLAMMATION OF THE SPLEEN, OR SPLENITIS 

Splenitis occurs in a variety of conditions, and may present itself 
in several forms, among which the acute enlargement of the spleen of 
infectious diseases and localized splenitis, or abscess of the spleen, 
are the principal. 

Diffuse Splenitis. — The splenic enlargement of infection occurs 
particularly in typhoid fever, malaria, septicemia, typhus, and relapsing 
fevers; and less markedly in pneumonia, scarlet fever, small-pox, and 
influenza. In the earlier stage the spleen is simply congested and pre- 
sents a dark-red color; is firm, and the capsule more or less distended. 
On section, the Malpighian bodies are usually obscured, and there may 
be visible areas of hemorrhagic extravasation. Microscopically at this 
stage the blood-vessels are all found overdistended, and the spaces 
within the splenic pulp are filled with red and white blood-corpuscles. 



446 



A TEXT-BOOK OF PATHOLOGY 



If the process has continued for some time, pigment masses and de- 
generated corpuscles are visible, but there are as yet no evidences 
of inflammatory hyperplasia of the splenic pulp or stroma. 

As the process advances the spleen may become softer and may 
be quite diffluent. On section, the substance is now found to be lighter 
in color, the Malpighian bodies are distinct, and, particularly in violent 
septic cases, are decidedly prominent, presenting themselves as yellow- 
ish-gray punctae, somewhat resembling miliary tubercles. The capsule 
of the organ may still be tensely distended, but in other cases is wrinkled, 
as if some shrinkage of the spleen had occurred in the change from the 
first stage of congestion to that of well-defined inflammation. Micro- 
scopically there is now apparent a great increase of the cells of the 
splenic pulp, particularly of those constituting the Malpighian bodies. 
That this increase is partly at least due to active proliferation is known 
from the abundance of mitoses. There is also hyperplasia of the stroma 
and trabecular, and of the endothelial cells of the spaces. 

In still later stages signs of degeneration may become prominent. 
This is apparent in the increasing softening of the organ, while under 
the microscope there are found cellular degenerations leading to the 
formation of detritus, to fragmentation of the nuclei of the cells, and to 
pigmentation by disintegration of red blood-corpuscles. 

Terminations. — Most frequently complete resolution occurs. Some- 
times, however, persistence of the inflammation is noted; and, when 
repeated attacks of the infection occasion repeated attacks of splenitis, 
chronic inflammatory hyperplasia is the result. This is especially 
marked in the "ague-cake" spleen of malaria. Spontaneous rupture 
or rupture from slight trauma may result from the softened and dis- 
tended condition of the organ. Finally, suppuration may ensue, either 
in the form of a diffuse softening and purulent infiltration of the entire 
organ, or in the form of a localized abscess beginning at the point of 
greatest involvement. 

Circumscribed Splenitis, or Abscess of the Spleen. — This may 
be the termination of an acute diffuse splenitis, particularly in septi- 
cemia and typhoid fever; or it may be caused by extension of diseases 
of neighboring structures, by septic embolism, or traumatic injuries. In 
the last case, the mechanical injury of the spleen merely furnishes suit- 
able conditions for the action of bacteria conveyed to it through the cir- 
culation, or the spleen is actually penetrated and infected. Occa- 
sionally abscess may result from the perforation of gastric ulcers or from 
the extension of other inflammations in the vicinity. An important 
group of cases is that in which the abscesses are embolic and metastatic 
(Fig. 181). Such cases are met with in malignant endocarditis or throm- 
bosis of the heart or aorta, and in cases of pyemia following other in- 
fective conditions. The first effect of the embolism is a hemorrhagic 
or anemic infarction, but this soon undergoes suppurative softening, 
beginning at the apex of the infarct. Metastatic abscesses are most 
common near the surface of the organ and are usually multiple, though 
a single cavity occupying the greater part of the organ may occur. 



DISEASES OF THE LYMPHATIC TISSUES 



447 



Small collections may become absorbed or inspissated, leaving a necrotic 
or cheesy collection as a residue. Larger collections may be discharged 
by perforation into the stomach or intestines, or they may break into 
the peritoneal or pleural cavity, causing septic peritonitis or pleuritis. 

Chronic Inflammation or Chronic Hyperplasia of the Spleen. 
— Attention has already been called to the slow hyperplasia of the con- 
nective tissue and sometimes of the splenic pulp occurring in conse- 
quence of chronic passive congestion and of repeated attacks of acute 
splenitis. The spleen is large in size and firm. The capsule is often 
tensely distended and may be greatly 
thickened. The thickening is either 
diffuse or circumscribed, patches of 
almost cartilaginous hardness occur- 
ring in the latter case. Attachments 
by fibrous adhesions may fix the 
spleen to the diaphragm or the neigh- 
boring organs. On section the spleen 
is found dark in color from the pres- 
ence of abundant pigment, and the 
excess of fibrous tissue may be visible 
to the naked eye. Microscopically, 
increased thickness of the fibrous 
trabecular, hyperplasia of the con- 
nective tissue about and within the 
follicles and that of the walls of the 
small blood-vessels, and pigmenta- 
tion with altered blood-pigment are 
the conspicuous features. 

A somewhat different form of 
chronic hyperplasia is dependent 
upon syphilis, especially upon the 
congenital form. In this the appear- , Fig 181.— Embolic abscess of the 

, , , ... spleen (from a specimen in the Museum 

ances are much the same as m the of the Philadelphia Hospital), 
cases following splenitis or conges- 
tion, but, as a rule, the color is somewhat lighter from the fact that the 
process is a slowly hyperplastic one without acute inflammatory or con- 
gestive manifestations. Somewhat similar appearances result from 
rickets. The indurative processes in the spleen following cirrhosis of 
the liver may be due at times to thrombosis of the liver veins, but this 
does not always exist. It has been suggested that circulating toxins are 
responsible. 

Splenic Anemia ; Splenomegaly. — These terms have been used to 
describe a clinical condition distinguished by chronic enlargement of the 
spleen due mainly to fibrosis beginning in the follicles, gastro-intestinal 
disturbances, a tendency to hemorrhages from the stomach, and later 
by progressive weakness and ascites. Anemia of chlorotic type may 
occur, especially in the hemorrhagic cases, but is not essential, and the 
name "splenic anemia" is, therefore, ill chosen. The development of 




448 



A TEXT-BOOK OF PATHOLOGY 



ascites is due to secondary cirrhosis of the liver. Cases presenting this 
association are designated Bantis disease. 

The so-called primary or idiopathic splenomegaly of Gaucher is an 
enlargement of the spleen due to accumulations of endothelial cells 
without much cirrhotic change, associated with enlargement of the 
liver, anemia, and pigmentations of the skin, or hemorrhages. The 
liver and lymph-glands may show the endothelial changes as in the spleen. 

The etiology and nature of these cases is probably varied. At 
autopsy some show merely chronic congestion of the spleen, others a 
more definite chronic hyperplasia, a few have been found to present 
a peculiar proliferation of the endothelium of the sinuses (see Tumors). 
Formerly splenic anemia was regarded as a splenic type of Hodgkin's 
disease. This view has been disproved by the absence of the usual 
histological features of the latter disease. 

ATROPHY AND DEGENERATIONS 

Atrophy of the spleen is very common in old age. The capsule 
is usually wrinkled and somewhat thickened, and on section the organ 
is more fibrous in appearance on account of atrophy of the splenic pulp 
and proliferation of the stroma. Thickening of the capsule some- 
times appears in the form of white plates of cartilaginous hardness, 
which result from inflammatory overgrowth of the capsule {perisplenitis 
cartilaginea) . 

Amyloid infiltration occurs more frequently in the spleen than in 
any other organ. The causes are those which lead to amyloid disease 
elsewhere. In most cases the degeneration begins in the Malpighian 
bodies, affecting the walls of the blood-vessels (Plate 5) and the lymph- 
oid elements. On section in such a case there are seen small round areas 
about the size of a currant-seed, of gelatinous, translucent appearance. 
These have been likened to grains of boiled sago, and the term sago 
spleen is not inappropriate. In other cases a more uniform involvement 
of the whole organ is noted, and the section presents the appearance of 
boiled ham or dried beef (bacony spleen). Considerable enlargement of 
the organ is noted in such instances, and the tissue is much harder than 
normal. Beginning amyloid degeneration may be difficult to determine 
microscopically, but is readily demonstrated by the microscopical stain- 
ing reactions. (See Amyloid Degeneration.) 

Hyaline degeneration has been observed in association with amy- 
loid and independent of the latter. It affects the small blood-vessels and 
the reticulum more particularly. 

Pigmentation is a very common result of chronic congestion as well 
as of repeated acute splenitis; the spleen in cases of cirrhosis of the liver 
and in chronic malaria is, therefore, habitually pigmented. The deposit 
occurs first in the walls of the blood-vessels and later throughout the 
splenic structure, either within the cells or lying free in the tissue. 
Occasionally pigment particles derived from the external world are 
deposited in the spleen. This is especially true of dust particles which 



PLATE 5 



9 



J% */-•••' **V~\y: 4 fv 



1 o; .- " 



Amyloid degeneration of the spleen, showing a degenerated Malpighian body; specimen 
stained with hematoxylin and eosin. 



DISEASES OP THE LYMPHATIC TISSUES 



449 



have reached the circulation from softened bronchial glands. In cases 
of diseases of other kinds leading to discharge of foreign bodies or tissue 
elements into the circulation, the arrest not rarely occurs in the spleen, 
and reactive congestion or inflammation with enlargement of the spleen 
may result (spodogenous splenitis). Pigmentation of the spleen is 
seen in progressive pernicious anemia and other conditions in which 
hemolysis occurs. The pigments resulting from the destruction of red 
corpuscles are deposited in the liver, spleen, and other organs. Biliary 
pigmentation of the spleen occurs in various forms of jaundice. Pig- 
ment is removed or at least ingested by endothelium, lying along 
trabecular and sinuses. Hematoidin is found in infarcts. 

Calcification occurs in the thickened capsule of chronic splenitis 
and in old infarcts, tuberculous or syphilitic areas, and occasionally in 
thrombi of the splenic vein. Parasitic cysts may be surrounded by 
calcification. 

LEUKEMIA AND HODGKIN'S DISEASE 

The spleen is usually involved in leukemia and occasionally in 
Hodgkin's disease. The former condition is primarily an affection of 
the bone-marrow (myeloid type) or of the lymphatic glands (lymph- 
atic type). In either case, however, the spleen is usually involved. 
In the earlier stages the organ is enlarged and soft, and on section 
exhibits evidences of intense congestion. Later, the characteristic 
hyperplasia of myeloid or lymphatic elements causes a lighter color or 
areas of lighter color between the more congested portions. Infarc- 
tions, sometimes of considerable size, and hemorrhagic or anemic and 
necrotic, may add to the variegated appearance of the surface of section. 
Histologically in myeloid cases there are found areas of myelocytic or 
myeloblasts hyperplasia, sometimes with giant cells and erythro- 
blasts, characteristic of myeloid structure. In lymphatic cases abundant 
lymphocytes replace the normal splenic tissue. 

In Hodgkin's disease the characteristic histological features (see 
Lymphatic Glands) may be found in the enlarged spleen. 

TUMORS AND PARASITES 

Sarcoma and Carcinoma. — Primary sarcoma of the round- 
celled or fibrosarcomatous variety has been observed. Secondary 
sarcoma, particularly melanotic sarcoma, is more common than the 
primary growth, and secondary carcinoma occurs. 

Endothelioma. — A few of the cases of the clinical syndrome called 
splenic anemia have presented a remarkable proliferation of the endo- 
thelium of the splenic sinuses, and authors have variously regarded the 
process as an endothelial hyperplasia or as endothelioma. In a case 
reported by Stengel the process strongly suggested a tumor. 

Cysts are occasionally discovered. They are small and are prob- 
ably due to dilatation of the lymphatic spaces, or to atrophy and cystic 
degeneration of the Malpighian follicles. 

29 



450 



A TEXT-BOOK OF PATHOLOGY 



Others are said to be due to an intracapsular injury and hemorrhage, 
with absorption of the solid parts and subsequent encapsulation. 
Lamina of clot may be found on the walls. Some authors believe that 
cysts may be due to an invagination of peritoneum. 

Fibroma, angioma, and lymphangioma are very rare. 

Parasites. — Linguatula rhinaria, echinococcus cysts, and cysticerci 
have been observed. 

INFECTIOUS DISEASES 

Tuberculosis of the spleen may occur in the form of minute miliary 
tubercles, which have a grayish translucent appearance, and are usually 
present in large numbers, especially near the cap- 
sule. They may be distinguished from enlarged 
Malpighian bodies by their greater opacity and 
their grayish rather than yellowish color. Tuber- 
culosis also occurs in the form of larger caseous 
nodules, especially in children (Fig. 182). In 
these cases there are seen nodular masses the size 
of a pea or cherry studding the surface and 
deeper structure of the spleen. This form is 
called Affenhiberculose by the Germans, from 
the resemblance of the large nodules to tubercles 
met with in monkeys. Histological examination 
proves the nodules to be composed of aggrega- 
tions of tubercles undergoing caseation. Prim- 
ary tuberculosis of the spleen has never been 
observed. 

Syphilis may present itself in the form 
of syphilitic gummata, which are usually mul- 
tiple and may be either small or large. They 
Large case- are distinguished by their central degenera- 
tion or by the fibrous tissue striations at the 
exterior. 

Diffuse hyperplasia of the spleen is a frequent or almost constant 
lesion of congenital syphilis. 

The spleen is the seat of secondary deposits in actinomycosis, glanders, 
and leprosy, the lesions following the type characteristic for these dis- 
eases. 

Perisplenitis. — The capsule of the spleen may be inflamed as a part 
of acute splenitis or from a peritonitis. It is usually of a fibrinous 
character and may resolve or continue into a chronic stage, in which 
case it may have adhesions to adjacent organs or extension into the 
trabeculse, or both. The capsule becomes gray and opaque. 




Fig. 182 
ous 

spleen of a child (Orth). 



tubercles 



The Lymphatic Glands 

Anatomical Considerations. — The lymphatic glands or nodes are 
accumulations of lymphadenoid tissue enclosed in a fibrous capsule, 



DISEASES OF THE LYMPHATIC TISSUES 



451 



into which a number of small afferent lymphatic vessels enter, and 
from which a somewhat smaller number of larger efferent lymphatic 
vessels emerge. The nodes are composed at the periphery of spherical 
lymphatic follicles made up of lymphadenoid tissue, and at the center;of 
medullary cords of the same structure. Under the outer capsule and 
alongside of the fibrous trabecular which dip down between the follicles 
and cords are spaces lined with endothelial cells, the lymph-sinuses. 
Through this system of channels the lymph conveyed by the afferent 
vessels filters to the hilum of the glands, where the efferent vessels 
take their origin. Histologically, the lymph-follicles present at their 
centers collections of somewhat large and pale-staining cells with 
numerous mitotic figures. These are the germ centers composed of 
lymphoblasts. Surrounding these are smaller and more deeply staining 
cells — lymphocytes. 

Functions of the Lymphatic Glands.— Two important functions 
of the glands are recognized : a filtering action and blood-cell formation. 
The filtering action of the glands is readily explained by the anatomical 
features described, and is exhibited by the accumulation of bacteria or 
pigment in the lymphatic glands adjacent to an infective lesion or a 
source of pigmentary deposit. What part the regional lymphatic glands 
may play in the local inhibition of infective processes by destroying 
micro-organisms arrested by them is a matter of theory rather than 
present knowledge. 

The blood-cell formation of the lymphatic glands is concerned 
with the production only of lymphocytes and the plasma-cells. Both 
of these cell forms are apparently derivatives remotely of the endo- 
thelium of the lymphatic vessels or sinuses, and more immediately 
of lymphoblasts. The lymphocytes are relatively small cells with 
deeply staining nuclei, a marked nuclear membrane, and a somewhat 
granular basophilic protoplasm. These are derived from lympho- 
blastic cells (such as are seen in the germ centers of the follicles) 
— larger cell forms with paler nucleus and protoplasm. From these 
forms under pathological conditions may be derived plasma-cells, which 
are mainly distinguished by the eccentric position of the nucleus and 
the deeply staining (basophilic) protoplasm. These cells are especially 
abundant in the round-cell infiltration of inflammation. 

Hemolymph Glands. — Certain of the lymphatic glands of the retroperitoneal region 
differ from ordinary lymphatic glands in having blood-sinuses instead of lymph-sinuses. 
These have been termed "hemolymph glands." Such glands are less frequently found 
in other situations, such as in the mediastinum, thymus region, cervical region, 
etc. They are usually embedded in fat tissue, and, as a rule, are near the wall of some 
large vessel. The number and size of the blood-vessels connected with these glands 
are remarkable, showing the relation to the hemic circulation. Transitional condi- 
tions between the typical lymphatic gland and the hemolymph gland are met with. 
Some of the glands resemble splenic tissue, and others the marrow tissue. Warthin 
suggests the terms "splenolymph" and "marrow-lymph gland." Pathologically these 
glands have been found congested or showing evidences of increased pigment forma- 
tion in various types of anemia. They appear to have an active hemogenic function 
in such conditions. 



452 



A TEXT-BOOK OF PATHOLOGY 



ATROPHY 

This condition of the lymph-glands occurs in old age and in various 
marasmic conditions. The glands suffer considerable diminution in 
size, the cellular elements being particularly affected; they are, therefore, 
hard, dry, and often irregular in shape. Fatty infiltration may occur 
simultaneously with atrophy, the gland in such cases preserving its size 
and having a decidedly fatty appearance. 

HYPERTROPHY 

This is so closely allied to the conditions designated by the name of 
"lymphoma" that it is difficult to separate the cases which might be con- 
sidered as strictly hypertrophy. In cases of experimental or surgical 
splenectomy, hypertrophy of the lymphatic glands has been observed. 
Chronic enlargement of the tonsils and generalized lymphatic enlarge- 
ment in status lymphaticus may also be considered as forms of hyper- 
trophy. 

STATUS LYMPHATICUS 

This condition is one in which there is a marked preservation after 
early infancy or childhood of the relative excess of lymphatic tissue that 
characterizes the earlier years of life. A pronounced feature of the 
anatomy of childhood is the richness in lymphatic tissue and the high 
percentage of lymphocytes in the blood. After the first few years, but 
especially after puberty, this excess of lymphadenoid structures disap- 
pears, but in certain individuals it persists. In such cases the term 
"status lymphaticus" is applied. Formerly this condition was regarded 
as closely identified with status thymicus, in which persistence of the 
thymus gland after the time of its normal atrophy is met with. Certain 
recent authors separate the two conditions, and certainly status lymphat- 
icus is much more frequently unaccompanied by persistent thymus than 
accompanied by it. 

Among the physical features of the lymphatic status are hypertro- 
phies of the lymphadenoid tissues of the pharynx, the back of the 
tongue, the nasal passages, enlarged tonsils, cervical lymphatic glands, 
Peyer's patches, etc. The blood-vessels are usually hypoplastic and the 
heart may be in the same condition. Enlargement of the spleen and a 
persistent thymus may be found. The blood presents the infantile 
excess of mononuclear elements (mononucleosis) , especially lymphocytes ; 
in some cases the bone-marrow remains persistently infantile (red) in 
type. In recent years particular attention has been called to a lack in 
development of the chromaffin system. The adrenals are deficient and 
the other structures containing chromaffin elements are more or less 
defective. To this lack of chromaffin substance, and the consequent 
deficiency of its secretions (adrenalin, etc.), may be due the low tension 
of circulation, and perhaps sudden death, which sometimes occurs. 

Certain writers describe as a separate form from the type above 
discussed, and which they regard as primary status lymphaticus, a second- 



DISEASES OF THE LYMPHATIC TISSUES 



453 



ary form which is developed in childhood or, later, in persons who had 
previously shown no abnormal structural conditions. Such secondary 
forms are said to occur as a result of rickets, syphilis, tuberculosis, and 
other infections, asthma and various diseases of the glands of internal 
secretion, such as Addison's disease, Graves' disease, myxedema, etc. 
The physical peculiarities are the same, but less pronounced than in the 
primary form. Rather too much weight seems to us to have been given 
to the blood condition (mononucleosis; lymphocytosis) in suggesting the 
existence of a status lymphaticus in some of these diseases. 

DEGENERATIONS 

Fatty infiltration is sometimes seen in cases of general obesity 
and also, as before mentioned, in atrophy of the glands. 

Amyloid infiltration is met with in cases of general amyloid dis- 
ease, and particularly in the cases in which the intestines are affected. 
The lymphatic glands may, however, be independently involved in 
cases of tuberculosis attended with suppuration. In such instances the 
adjacent lymphatic glands are most likely to suffer amyloid change. 
The morbid process rarely leads to marked alteration of the glands, but 
the amyloid material may be dem- 
onstrated by the staining reactions 
peculiar to it. The connective tis- 
sue of the trabecular and around 
the blood-vessels is first affected; 
later, the endothelial cells. 

Hyaline degeneration has 
been observed. It affects the 
blood-vessels and connective tissue 
of the glands. 

Calcification not infrequently 
forms the terminal condition in 
cases of necrosis or induration of 
the glands in consequence of tuber- 
culous or simple inflammation. 
There may be small calcareous granules scattered through the gland, or 
the entire gland may be infiltrated. 

Necrosis may occur in consequence of tuberculous or syphilitic 
affections, or of simple inflammation. In the former cases, particularly 
in tuberculosis, the center of the gland or the entire gland becomes 
cheesy and soft, often liquefying and discharging the contents by 
rupture of the capsule. In consequence of simple inflammation, as in 
certain infectious fevers (typhoid, diphtheria, scarlet fever), a different 
form of necrosis is met with, areas of the gland becoming soft, pulta- 
ceous, and sometimes putrid. The gland may rupture, discharging its 
contents, or absorption of the liquid with inspissation and a pseudo- 
caseous form of degeneration may result. Finally, the degenerated 
area may become calcareous. 




Fig. 183. — Anthracosis of a bronchial 
lymph-gland (Orth). 



454 



A TEXT-BOOK OF PATHOLOGY 



Pigmentation may follow acute inflammations or traumatism of 
the glands, the extravasations of blood occurring in such conditions 
leading to hematogenous pigmentation. The blood-pigment occurs in 
granular masses within the cells of the stroma or within the lymphatic 
cells themselves. Blood pigmentation may also occur in the glands 
adjacent to areas of hemorrhagic extravasation, the pigment in such 
cases reaching the glands through the lymphatic vessels and being de- 
posited in the lymph-sinuses, or even in the follicles and cords. Analo- 
gous pigmentation from external sources may result from tattooing, and 
occurs regularly in the bronchial glands as the result of the inhalation 
of various dust-particles which penetrate the walls of the bronchioles 
and alveoli, and eventually find their way to the bronchial glands 
through the lymphatic stream (anthracosis) (Fig. 183). The glands may 
be completely black in such cases, and the lymphatic circulation through 
them may be obliterated. Secondary inflammatory changes result in 
most cases (see p. 455). 

INFLAMMATION; LYMPHADENITIS 

Acute lymphadenitis is commonly secondary to inflammations in 
the neighborhood, the irritants being carried by the afferent lymph- 
atics. Sometimes direct extension of inflammation by contiguity of 
structure may lead to involvement of the lymphatic glands. Occa- 
sionally lymphadenitis is seemingly primary in cases in which the in- 
fective irritants have caused no lesion at the portal entrance to the 
body. 

Pathological Anatomy. — The glands become enlarged, hyperemic, 
and considerably infiltrated with liquid. When the inflammation is 
intense there may be minute hemorrhages. Microscopically, the 
lymph-sinuses are found distended with cells — leukocytes, red blood- 
cells, and proliferated and desquamated endothelial cells from the lining 
membrane of the sinuses. The follicles and cords are increased in size 
from infiltration and probably also from proliferation of the lymphoid 
cells. The process may become arrested and resolution to the normal 
condition may ensue. If mild inflammation of this character has con- 
tinued for a great length of time, or if the condition is repeated, hyper- 
plasia of the trabecular connective tissue, of the blood-vessels, and of the 
capsule of the gland may lead to a termination in chronic enlargement 
and induration of the glands. The changes in the sinuses are spoken of 
as "sinus catarrh." The proliferated lining endothelial cells in some 
places dominate the field. They may have more than one nucleus; 
they are actively phagocytic. 

In cases of greater intensity of the infective cause, necrotic or 
suppurative changes may occur. In the cases of necrosis such as occur 
in typhoid fever and in diphtheria there may be noted small spots of 
yellowish-white color in the hyperemic glands, and subsequently these 
undergo well-marked necrosis. Complete necrotic softening and even 
rupture of the gland may ensue, or, if the necrosis remains limited in 



DISEASES OF THE LYMPHATIC TISSUES 



455 



extent, inspissation and sometimes calcification may terminate the 
process. 

Suppurative lymphadenitis is not uncommon. It is seen in the 
glands below Poupart's ligament in cases of infective wounds of the 
leg; in the inguinal glands as a result of chancroid or gonorrheal urethri- 
tis; in the glands of the neck in association with diphtheritic, scarlatinal, 
or other inflammations of the throat, or following erysipelas; in the 
axillary glands as a result of wounds of the arm; and in the internal 
lymphatics in various infective diseases. The term bubo is applied to 
suppurative lymphadenitis of superficial glands. Of particular interest 
is the tendency to this condition in the plague of the East, or the bubonic 
plague (q. v.). 

Pathological Anatomy. — The changes noted in the gland at the 
outset are similar to those in the simple inflammations, but under the 
microscope a greater accumulation of leukocytes is apparent, and the 
gland tends to soften, with the formation of more or less creamy pus. 
The capsule may prove resistant for a time, and reactive inflammation 
around it may establish an additional wall. A single gland of a group 
may be affected, but more commonly the several glands are together 
involved. Eventually rupture may take place, but in instances in which 
the process has been circumscribed, inspissation of the pus and, finally, 
calcification may occur. 

In the most intense forms of lymphadenitis hemorrhagic or gan- 
grenous conditions are developed. These acute inflammations usually 
have associated with them an infiltration and edema in the surround- 
ing tissues (perilymphadenitis) . 

Chronic lymphadenitis leads to induration with enlargement. 
It occurs as the result of repeated acute attacks or in consequence of 
long-continued irritation by particles carried to the lymphatic glands 
from some focus of disease. 

Pathological Anatomy. — As a rule, the process affects the connective- 
tissue elements of the gland in particular, and there results a consider- 
able amount of induration, sometimes associated with atrophy or 
necrosis of the proper lymphoid structure. Occasionally, however, the 
lymphoid elements themselves are hyperplastic, and the normal relation 
of fibrous tissue, follicles, and medullary cords is preserved. 

Microscopically, the overgrowth of the connective tissue springing 
from the trabecular, around the blood-vessels, and of the reticulum of the 
pulp is apparent. This may consist of round cells and fibrous connective 
tissue, or there may be a tendency to the formation of epithelioid cells 
and even giant cells. 

Pathological Physiology. — Inflammations of the lymphatic glands 
are the result of the arrest of irritants of various sorts carried to the 
glands in the lymphatic channels. This arrest not unlikely serves 
the purpose of a protection against general dissemination of -irritants, 
and may be of great importance in this way. Complete occlusion of 
the lymph-sinuses by deposition of solid particles (as coal-dust) or by 
disease of the glands may obstruct the lymphatic flow entirely, and a 



456 



A TEXT-BOOK OP PATHOLOGY 



retrograde inflammatory process may result from the damming back of 
infected lymph or from extension of disease along the lymphatic chan- 
nels. 

INFECTIOUS DISEASES 

Tuberculosis of the lymphatic glands is due in nearly all cases to 
infection by bacilli reaching the gland through the afferent lymphatics, 
though occasionally hematogenous infection occurs. Under the heading 
"tuberculosis" we must include what the older writers designated as 
scrofulous glands, for in the majority of such cases, if not in all, the 
disease is essentially tuberculosis, though the mode of infection is not 
always apparent. 

Pathological Anatomy. — The first visible change is the formation of 
small grayish nodules in the gland, and sometimes the eruption of these 




Fig. 184. — Tuberculosis of lymph-gland, showing early miliary tubercle and hyaline 

connective tissue. 

is attended with hyperemia and inflammation. Later, these tubercles 
increase in size and undergo caseous changes (Fig. 185) as elsewhere, 
and eventually the entire gland may be converted into a cheesy mass, 
which may liquefy and not rarely discharges through the ruptured cap- 
sule. Microscopically, the first appearance is that of gray tubercles 
containing giant cells and epithelioid cells, surrounded by-a zone of 
round cells (Fig. 184). Later, the characteristic appearances of hyaline 
transformation and of caseation are observed. Sometimes the glands in 
tuberculosis become enlarged and harder than normal, and present 



DISEASES OF THE LYMPHATIC TISSUES 



457 



areas of grayish color, but do not tend so markedly to undergo necrosis. 
In these instances the microscopical examination presents foci com- 
posed for the most part of epithelioid cells, and much less abundant in 




Fig. 185. — Tuberculous lymphatic gland: a, a, Recent tubercle with giant cell (c, c); 
a lt caseous tubercle with giant cell (cj ; 6, 6, b, lymphadenoid tissue; d, d, d, epithelioid 
cells (Ziegler). 

round cells than are tuberculous tissues as a rule (Fig. 186). Giant 
cells may be wanting, or a few may be found on prolonged search. 
The histological picture in these cases somewhat suggests sarcoma, and 




Fig. 186. — Tuberculous lymphatic gland: a, a, Lymphadenoid tissue; b, b, large round 
cells (epithelioid); c, c, large spindle cells (Ziegler). 

the clinical as well as pathological findings have led some to regard 
cases of this type as Hodgkin's disease, and erroneously to conclude that 
Hodgkin's disease is really a form of tuberculosis of the lymphatic 
glands. 



458 



A TEXT-BOOK OF PATHOLOGY 



Scrofula. — The tuberculous nature of scrofulous lymphadenitis 
was first shown by demonstrations of the infectiousness of the soft- 
ened glandular material when injected into animals. The micro- 
organisms themselves may be demonstrable in the earlier stages in the 
epithelioid or giant cells, or lying between these; but when the process 
is at all advanced it is extremely difficult or impossible to demonstrate 
bacilli. 

Individual Groups of Glands. — Among the more commonly affected 
groups of glands are the cervical (Fig. 187), the bronchial, and the 
mesenteric. Tuberculous cervical glands occasion considerable tumors 




Fig. 187. — Tuberculous lymphadenitis of the cervical glands (from a case in the Children's 

Hospital). 

in the neck, and it is these in particular that have been classified as 
scrofulous. Not rarely they advance to complete softening and rupture 
on the surface. Sometimes, however, they penetrate deeply, and may 
rupture into the trachea or esophagus, or into the pleural cavity. The 
mode of infection is rarely apparent, but in many cases no doubt the 
micro-organisms enter through the mucosa of the mouth or pharynx, 
or the tonsils, where they may or may not first occasion specific lesions. 

The bronchial glands are affected very frequently in cases in which 
the bacilli, entering through the lungs, have left no trace of tubercu- 
lous disease at the portal of entrance; while in cases of actual tubercu- 



DISEASES OF THE LYMPHATIC TISSUES 



459 



losis of the lungs the bronchial glands are quite constantly involved 
(Fig. 18S). The glands are usually cheesy and may become calcareous, 
but softening not rarely occurs. Perforation of one of the bronchi may 
lead to acute bronchogenetic tuberculosis of the lungs; or the softened 
gland may discharge into a large vein and thus occasion disseminated 
miliary tuberculosis. 

The mesenteric glands are es- 
pecially involved in children, this 
condition being known as tabes 
mesenterica. The infection occurs 
through the intestinal tract, and 
has sometimes been shown to be 
due to the ingestion of infected 
milk or meat. The intestines may 
first suffer, or the bacilli may 
penetrate the intestinal mucosa 
without causing local lesions. 

Syphilis. — Enlargement of 
the lymphatic glands may occur 
in the vicinity of the initial lesion 
during the primary period; and is 
habitually present in all parts of 
the body during the secondary 
period, the post-cervical, axillary, 
inguinal, and epitrochlear groups 
being most characteristically in- 
volved. The glands are hard, and Fig. 188.— Tuberculous lymphatic glands 
, , "r « at the bifurcation of the trachea (from a 

do not tend to SOtten or SUppu- specimen in the Museum of the Philadelphia 

rate. Microscopically, there is Hospital), 
found proliferation of the con- 
nective-tissue elements throughout the gland, with some endothelial 
hyperplasia, giving pictures very suggestive of tubercles minus giant cells. 

In the tertiary period gummata (bubo tertiaris) may be observed, 
especially in the lymphatic glands adjacent to the diseased viscera. 

Leprosy and actinomycosis occasionally involve the lymphatic 
glands. (See General Pathology.) 

LEUKEMIA AND HODGKIN'S DISEASE 

It is difficult to classify these diseases, which in some respects appear 
to be related to pure hypertrophies, while in other features (mainly 
clinical) they suggest infections. Finally, there are certain facts which 
indicate a close kinship with tumors, as, for example, the similarity in 
histological features, the malignant nature of the diseases, the wide- 
spread lesions (metastasis?), and the fact that certain accepted tumors 
(chloromata) are accompanied by a leukemic character of the blood. 
For all of these reasons leukemia and Hodgkin's disease are here con- 
sidered between hypertrophy and infections on the one hand, and tumors 
on the other. 




460 



A TEXT-BOOK OF PATHOLOGY 



Leukemia. — The lymphatic glands are especially involved in the 
type of leukemia designated lymphatic, which usually, if not always, 
originates in the lymphatic glands. The view formerly held by many 
that all forms of leukemia originate in the bone-marrow was based upon 
an erroneous interpretation of the derivation of the cells in the blood 
and bone-marrow in certain cases. These cells, instead of being lympho- 
cytic, were myelocytic in nature, and the supposed lymphocytic process 
is now recognized as myelocytic or myeloblastic. 




Fig. 189. — Hodgkin's disease, showing marked enlargement of the glands of the right 
axilla, with consequent dropsy of the arm; less marked involvement of the submaxillary, 
cervical, and inguinal lymph-glands. 

The glands in lymphatic leukemia may be uniformly large in all 
parts of the body, or those of certain groups, such as the cervical, axillary, 
mediastinal, or inguinal, may be specially involved. Macroscopically, 
the glands are usually fairly firm, sometimes quite hard, or in other 
cases soft; are not greatly fused together when a whole group is affected; 
and on section the substance presents a grayish, pinkish to yellowish 
color. Areas of softening or hemorrhage may occur in exceptional cases. 

Histologically, the whole gland is uniformly infiltrated with lympho- 
cytic and lymphoblastic cells closely packed together and eradicating 



PLATE 6 




-.J.DZChs.S'?- 



Hodgkin's disease of the Reed type. The illustration shows various stages of the 
disease process. In the upper left corner there is hyperplasia of large epithelioid cells 
among the small lymph-cells. To the right of this, in what is probaby a sinus, there 
is hyperplasia of the large mononuclears, an excess of eosinophiles, fibroblasts, and fibers. 
Below these two sections of the picture are found masses of large mononuclears, sepa- 
rated by a connective-tissue framework, in which are also polymorphonuclears, eosino- 
philes, and polynuclear cells. At the bottom there is great increase of the fibrous tissue 
surrounding and distorting the cells. 



DISEASES OF THE LYMPHATIC TISSUES 



461 



all signs of the normal structure of the gland (follicles, medullary 
cords and sinuses). Sometimes the gland may be only partially involved, 
and the unaffected portion may then exhibit more or less normal histo- 
logical features. The walls of small blood-vessels are frequently pene- 
trated by the lymphocytic proliferations, which perhaps accounts for 
the entrance of the cells into the circulating blood. Similar histological 
features are found in the spleen and bone-marrow, and to a less extent 
in the liver and various other organs. 

Certain investigators have described cases with precisely the same 
histological features, but without the leukemic blood-picture, and have 
proposed names such as aleukemic lymphedema or lymphadenosis. That 
such cases may occur is easily understood when it is recalled that the 
blood-picture may become practically normal, either spontaneously or 
under treatment, without any notable change in the size of the glands or 
spleen. 

Hodgkin's Disease. — It is difficult to define this affection accu- 
rately, either clinically or pathologically, though a certain histological 
picture seems to be fairly distinctive (Plate 6). 

Macroscopically, Hodgkin's disease presents considerable enlarge- 
ments of certain groups of lymphatic glands, notably the cervical, 
axillary, and inguinal. Other groups may, however, be similarly in- 
volved. The glands are more or less fused together, though rarely to a 
single uniform mass. Exceptionally, the glands may be quite separate 
from one another. On section, the substance is more or less firm, of 
yellowish or grayish color, and not infrequently exhibits areas of necrosis. 
Histologically, there are found numerous elongated (fibroblastic?) 
cells, often arranged in a somewhat trabecular manner, between which 
lymphocytic elements are found in variable abundance. In some cases 
the most striking feature of the histological picture is the large number 
of eosinophile cells seen in the section. Giant cells are sometimes fairly 
numerous. There is a fine fibrosis between the cells. Here and there 
will be found a large palely staining cell like a large endothelial cell, 
sometimes with more than one nucleus or occasionally a ring of nuclei, 
suggesting an origin from the compression of a lymph-channel. 

Similar histological features are observed in the lesions of the spleen 
and liver met with in Hodgkin's disease. 

Tumors 

lymphoma, lymphadenoma; lymphosarcoma 

Lymphoma or lymphadenoma is a benign tumor affecting the 
lymphatic glands of a single group, or occurring in a more generalized 
form. Masses, sometimes of considerable size and of variable con- 
sistency {hard and soft lymphoma), are formed, but the process does not 
extend to surrounding tissues nor by metastasis to distant parts. Histo- 
logically, the growth presents the usual features of lymphadenoid 
tissue with more or less conspicuous hyperplasia of the reticular cells 
and endothelia in some cases (hard lymphoma). 



462 



A TEXT-BOOK OF PATHOLOGY 



It is extremely difficult to differentiate these growths from chronic 
lymphadenitis or lymphatic hypertrophy. The basis on which the 
distinction is made is rather the absence of adequate cause and the 
excessive growth of the glandular enlargements than any histological 
features. It must be recalled that very marked enlargements of lymph- 
atic glands may be found in the neck or elsewhere in association with 
long-continued irritations, such as bad dentition or oral infections. In 
these cases it is difficult to determine whether the glandular process is 
inflammatory, infectious, or neoplastic. 

Lymphosarcoma differs from lymphoma mainly in its manifest 
tendency to extend beyond the limits of the affected gland or group of 
glands to surrounding structures, and by metastasis to various parts of 
the body. The histological structure differs from that of lymphoma 
only in the less typical features of lymph-gland architecture. There 
is less differentiation of follicles, sinuses, and a more uniform undiffer- 
entiated lymphadenoid structure. Lymphosarcomata are especially 
common in early life, and occur in the cervical glands, tonsils, and 
mesenteric glands. Chloroma (see pp. 188 and 466) is a closely allied 
form of growth characterized by its greenish color. 

Endothelioma of the lymph-glands may occur, according to Ewing, 
but it is difficult to determine in any given case whether it be truly 
neoplastic or secondary to a granulomatous disease of the nodes. A 
long-continued inflammation of the gland may occasion a neoplastic 
growth of the endothelium and overshadowing or obliteration of the 
lymphadenoid tissue. 

Sarcoma. — Other forms of sarcoma are sometimes met with as 
primary localized new growths of the lymphatic glands. Such are not 
rarely seen in the mediastinum. In these instances the capsule of the 
gland is penetrated and local extension to neighboring glands and other 
surrounding structures is commonly observed, but the entire group of 
glands is not, as a rule, affected. General metastasis may occur, but 
affects the larger organs rather than the lymphoid tissues. Round- 
cell, spindle-cell, alveolar sarcoma, and endothelioma are the forms 
described. Secondary sarcoma occasionally involves the lymphatic 
glands. 

Carcinoma is always secondary, the regional lymphatic glands being 
the most frequent seat of secondary cancer. The metastatic deposits 
are first seen in the peripheral lymph-sinuses of the gland, but later 
enlarge and may invade the whole gland or spread beyond the capsule. 

Bone-marrow 

Anatomical Considerations. — The marrow of the bones is a tissue 
composed of a reticulum of connective-tissue cells, supporting a rich 
network of capillaries and venules of unusual width. The cells proper 
of the marrow are rounded and vary greatly in size. They contain a 
clear nucleus, a slightly acidophilic protoplasm, and many of them 
neutrophilic granules. In addition to these myelocytes there are occa- 



DISEASES OF THE LYMPHATIC TISSUES 463 

sional giant cells {megakaryocytes or myeloplaxes) lying near the bony 
trabeculse; also nucleated red corpuscles, non-nucleated red corpuscles, 
and large cells enclosing corpuscles. After the first few years of life 
the marrow of the long bones loses its reddish color and becomes more 
or less yellow, and there is then found, microscopically, a great pre- 
ponderance of fat-cells. The marrow of the vertebra?, sternum, ribs, 
and other flat bones remains more or less red throughout life, and 
islands of red marrow tissue may also be found in the marrow of the long 
bones in later years. 

The marrow cells are descendants of the endothelial cells of blood- 
vessel walls. From these are derived somewhat large rounded cells 
containing a relatively large nucleus and having a basic non-granular 
protoplasm. These cells, termed myeloblasts, are the mother-cells from 
which the myelocytes (neutrophilic, eosinophilic, and basophilic) take 
their origin. This stage of the process of marrow-cell and blood forma- 
tion is seen only in the latter months of fetal life and for a short time 
after birth; and pathologically in certain diseases affecting the blood. 
Soon after birth the myeloblasts are no longer found, and the myelocytes 
then represent the earliest phase in the process of leukocyte formation. 

The red blood-corpuscles of the blood (erythrocytes) also trace 
their origin from the endothelial cells of blood-vessels. In the fetal 
marrow and under certain pathological conditions in later life may be 
found certain large hemoglobin-containing cells with a large pale nucleus 
(primary erythroblast or megaloblast) which are probably direct deriva- 
tives of the endothelial cells. In later periods of life a rounded, baso- 
philic cell, containing a rather small and dark-staining nucleus, is the 
intermediary stage between the endothelial cell and the hemoglobin- 
containing erythroblasts. The latter also contain a darker and smaller 
nucleus than that of the "primary erythroblast." In the ultimate 
formation of non-nucleated red cells the nuclei of the erythroblasts un- 
dergo a process of pyknosis and karyorrhexis. The older idea of nuclear 
extrusion is probably incorrect. 

In addition to the important role of blood formation the bone-mar- 
row doubtless also plays some part in the defensive processes against for- 
eign invaders. The large giant cells are occasionally greatly increased in 
size and number and exhibit active phagocytic properties in conditions 
attended with marked leukocytosis; myelocytes are greatly increased 
in number in certain infections, and sometimes myeloblasts become 
conspicuous. Finally, a more or less -mechanical role may be indicated 
by the lodgment of large numbers of malarial plasmodia or other micro- 
organisms in the marrow. 

DEGENERATIONS 

Fatty Infiltration. — The fat which occurs normally in the marrow 
may be excessively developed in conditions of general obesity, but also 
at times in marantic individuals, or as a result of atrophy of the bony 
tissues. 



464 



A TEXT-BOOK OF PATHOLOGY 



Mucoid degeneration is occasionally seen, and necrosis may form 

a part of the processes of inflammation. 

Pigmentation occurs in the bone-marrow in cases of destruction of 
blood, as in malaria or various hemolytic toxemias. 

ATROPHY 

Atrophy of the bone-marrow is not infrequent in old age or in 
marasmic conditions. With this atrophy there may occur a gelat- 
inous or mucoid transformation. 

HYPERTROPHY 

Hypertrophy of the bone-marrow occurs in various conditions in 
which an increased functional activity is required (1) to replace the 
cellular elements of the blood in case of hemorrhage or blood destruc- 
tion, or (2) to provide greater numbers of certain cells in cases of infec- 
tion. The gross appearance of the bone-marrow and its histological 
features differ considerably in different cases. 

In anemic conditions resulting from repeated losses of blood or from 
hemolytic agencies the bone-marrow frequently exhibits a change from 
the adult (yellow or fatty) to the fetal or infantile type. In extreme cases 
the marrow of the long bones may be uniformly altered and sometimes is 
quite dark red in color; in less pronounced cases islands of pink or red- 
dish color are scattered through the unaltered fatty marrow. The 
highest grade of transformation is seen in typical instances of perni- 
cious anemia. Histologically, the marrow in the affected areas contains 
numerous nucleated red cells, many with mitotic nuclei, and also many 
myelocytes of different types and sometimes the primary myeloblasts. 
In pernicious anemia, in addition to these elements, there are found the 
primary erythroblasts or megaloblasts, and the spleen, liver, and lymph- 
atic glands may contain areas of myeloid (myelocytic) tissue. The 
sharp distinction between various milder anemias and pernicious anemia 
here suggested is difficult to establish in many cases, and all investigators 
are not in agreement that there is a fundamental distinction, some 
holding that the marrow changes differ only in degree. 

In infectious conditions, such as typhoid fever, pneumonia, strep- 
tococcus and staphylococcus infections, the marrow is the seat 
of marked changes. Areas of necrosis, degenerative changes in the 
blood-forming cells, and edema indicate the destructive effects of the 
infection, while hyperplastic processes are evidenced by large numbers of 
myelocytes, sometimes (especially in typhoid fever) myeloblasts and 
large numbers of phagocytic cells (megakaryocytes). Similar combina- 
tions of necrotic or degenerative processes and compensatory hyper- 
plasia are found adjacent to metastatic tumors invading the bone- 
marrow. 

The Bone=marrow in Leukemia. — The pathological changes in 
the bone-marrow as well as in other situations (liver, spleen, lymphatic 



PLATE 7 




so 



DISEASES OF THE LYMPHATIC TISSUES 



465 



glands) are difficult to classify, but are included under the heading hy- 
pertrophy because the conspicuous feature in the histological changes 
is the hyperplasia of the blood-forming cells. It is difficult, however, to 
distinguish the lesions of the marrow from those in certain conditions 
quite generally recognized as tumors (myeloma, chloroma), and even 
the composition of the circulating blood may be quite the same in some 
of these cases (chloroma) as in typical instances of leukemia. 

The bone-marrow in myelogenous leukemia presents a variegated 
appearance. Sometimes it is reddish, more often grayish or mottled, 
and occasionally quite yellowish (pyoid). Histologically, the conspic- 
uous feature is the abundant hyperplasia of myelocytic cells. These, 
like the myelocytes in the circulating blood, may vary considerably 
in their size and staining reactions. The typical neutrophilic myelocytes 
are most abundant, but eosinophilic and basophilic forms, as well as 
non-granular cells and occasionally forms containing two different sorts 
of granules, may be observed. The red-corpuscle-forming elements are 
rather inconspicuous even in comparison with normal bone-marrow. 
In myeloblastic leukemia (formerly designated acute lymphatic leu- 
kemia) the basophilic myeloblasts form the predominating histological 
element. 

The secondary foci of leukemic change (seen in the spleen, liver, 
lymphatic glands, and in various other organs) have a similar structure 
and represent local hyperplasis of marrow cells — either metastatic or 
originating locally' from reversion of endothelial cells of the blood- 
vessels to their embryonal condition and potency. 

In lymphatic leukemia the bone-marrow may present a quite similar 
macroscopical appearance, but histologically the myeloid elements are 
inconspicuous, while lymphoid cells constitute the bulk of the patho- 
logical areas. (See further under Lymphatic Glands.) 

INFLAMMATION 

Osteomyelitis, or inflammation of the marrow, is infectious in 
nature, and may occur in the course of various diseases, such as typhoid 
fever, relapsing fever, small-pox, septicemia, and the like; or as a result 
of traumatism and direct infection. Staphylococci and the typhoid 
bacillus (in typhoid cases) are the most frequent organisms encoun- 
tered. The marrow disease may be the only expression of an infection 
which has arisen in an obscure manner (cryptogenetic osteomyelitis) . In 
the cases occurring in the course of infectious diseases the changes are 
comparable to those which occur in the spleen under the same circum- 
stances. The marrow assumes a redder color than normal, and it may 
be studded with punctate hemorrhages. In other cases areas of necrosis 
and granular degeneration of the cells may be present, and increased 
numbers of white blood-corpuscles may be discovered. Large phago- 
cytic cells may be conspicuous. Sometimes the marrow is quite purulent. 
(See Diseases of Bone.) 



30 



466 



A TEXT-BOOK OF PATHOLOGY 



TUMORS 

The bone-marrow may be invaded by extension of tumors involving 
the bone, or may be the seat of metastatic growths, especially carcinoma. 
Greater interest, however, attaches to the primary tumors of the bone- 
marrow, which may be included under the general terms "myeloma" 
and "chloroma." 

Myeloma. — This occurs in the form of multiple primary growths 
involving the vertebrae, ribs, and, somewhat less frequently, the long and 
flat bones. The growths are grayish, yellow, and sometimes pink or 
quite deep red in color; sometimes by confluence a uniform growth 
occupies the whole marrow cavity. The surrounding bone sometimes 
becomes eroded and spontaneous fractures may occur. Metastasis does 
not occur. Histologically, myelomata are usually composed of myelo- 
cytes (granular or non-granular), but in some cases have been made up 
entirely of plasma-cells (plasmocy toma) . In rare instances erythroblasts 
may be conspicuous. Sometimes the tumor is greenish (myelocytic 
chloroma). The blood in myeloma rarely if ever presents leukemic 
features, but a striking clinical feature is the presence of Bence-Jones' 
albumin in the urine. 

Chloroma. — This term is applied to tumors presenting a greenish 
appearance on section, and involving the bone-marrow as well as the 
lymphatic glands, thymus, and the lymphatic tissues along the gastro- 
intestinal tract. The periosteum of the bones of the head and face is 
•an especially common seat. Histologically, two forms may be distin- 
guished: a lymphoidal, in which large lymphocytic cells make up the 
substance of the growth, and a rarer form, the myelocytic, in which the 
cells are of the bone-marrow type. The cause of the green color is 
unknown. Sometimes parts of the growths or certain of the metastases 
fail to present the green color seen elsewhere. An interesting feature 
is the leukemic character of the blood, which suggests the close relation- 
ship of leukemia to processes manifestly neoplastic. 



CHAPTER III 



DISEASES OF THE CIRCULATORY SYSTEM 
The Heart 

Development of the Heart. — At the earliest period of fetal life the 
heart is represented by a hollow tube, lying toward the ventral aspect 
of the neck. Later this assumes an S shape, and still later a transverse 
constriction marks the position which the auriculoventricular grooves 
subsequently occupy. Finally, vertical grooves divide the lateral 
halves into the respective auricles and ventricles; and the truncus 
arteriosus, which is at one of the ends of the primitive tube, becomes 
divided into two parts, forming the pulmonary artery and aorta. The 
separation of the cavities within is accomplished by the outgrowth of 
septa springing from the walls of the primary cavities. The septum 
dividing the ventricles is the first to appear, and springs forward from 
the posterior wall. Next a budding is seen in the position which is later 
occupied by the tissue between the auriculoventricular orifices of the two 
sides; still later the auricular cavity is divided into two parts by a 
process beginning at the lower and posterior part. The septum which 
divides the truncus arteriosus is essentially connected with or is a part 
of the septum which separates the ventricles. All of these changes 
begin from the seventh to the ninth or tenth week of fetal life. 

Anatomical Considerations. — The heart consists of three layers — 
the endocardium, muscular layer, and pericardium. The endocardium 
is the inner lining of the organ, and is composed of a layer of endothelial 
cells resting upon a stratum of connective tissue. It is continuous with 
the lining membrane of the arteries, and by duplications forms the 
valves. The muscle of the heart is arranged in layers which run in differ- 
ent directions — circular, longitudinal, and obliquely. There is no con- 
tinuity of the musculature of the auricles with that of the ventricles, 
except in the case of the special muscle cells, which will be mentioned 
presently. The muscle of the two sides of the heart is in part con- 
tinuous. Thus both auricles and both ventricles have certain muscle 
layers in common, but in part, especially in the ventricles, the muscula- 
ture is wholly independent. 

In recent years much attention has been given to a separate system 
of muscle cells or fibers (the Purkinje cells) which are found just be- 
neath the endocardium in the auricles and ventricles. They are now 
known to make up a well-ordered system which begins with the sub- 
endocardial fibers in the right auricle where it is spread out widely. At 
the auriculoventricular junction it becomes contracted to a narrow band 
or cord (the bundle of His) which passes downward into the interven- 

467 



468 



A TEXT-BOOK OF PATHOLOGY 



tricular septum, in the upper part of which it divides into a right and 
left branch. These branches run to the respective ventricles and their 
fibers spread out under the endothelium, and eventually extend to all 
parts of the musculature. This system, composed of somewhat less 
completely differentiated muscle cells than those of the body of the heart, 
is. concerned with the conduction of impulses to contraction from the 
auricle to the ventricle. At two positions there are found nodes or 
massed cells of this tissue — one in the wall of the right auricle adjacent 
to the mouth of the superior cava, the other at the auriculoventricular 
junction. The former is now recognized to be the site where the rhythmic 
impulses that occasion the cardiac contractions originate. 

The fibers of the heart muscle are peculiar in being branched and in 
being devoid of a sarcolemma. The pericardium resembles the endo- 
cardium in structure. 

The blood-vessels supplying the heart muscle are branches of the 
coronary arteries. They divide and subdivide, and afford abundance of 
blood proportionate to the needs of so active an organ. Anastomosis be- 
tween the ends of the myocardial vessels is by no means perfect, so that 
infarcts occur the more easily. The lymphatic system is equally de- 
veloped. The nervous system includes numerous ganglionic centers in 
the furrows between the ventricles and between the auricles and ven- 
tricles. Other ganglion-cells are found within the muscle itself. 

Details regarding the gross structure of the organ need not be men- 
tioned here. The weight of the heart in the adult male is about 300 gm., 
in the adult female about 250 gm. The volume of the entire organ in 
the adult male is about 290 to 310 c.c, in the adult female about 260 
to 280 c.c. 

CONGENITAL DISEASES AND DEFORMITIES 

Abnormalities of the heart may be discovered in the newborn and 
are the result of developmental defects or, less commonly, of fetal endo- 
carditis and myocarditis. The older pathologists attributed to inflam- 
matory changes many of the conditions which more accurate knowledge 
of the development of the heart clearly indicates are the result of defects 
in development. 

Abnormality of Position. — The heart may retain its position high 
up toward the cervical region, and may even be entirely in the neck. 
Occasionally it is completely exposed or, merely covered with peri- 
cardium, lies immediately beneath the skin, the sternum in such cases 
being divided in the middle line. Sometimes it lies beneath the skin of 
the abdomen. 

Abnormality in Size. — Congenital smallness, or hypoplasia, of the 
heart and aorta is occasionally observed. Particular attention has been 
called to this condition in cases of chlorosis (see p. 434). 

Defective Development. — There may be complete absence of the 
heart in acardiac monsters. Sometimes the septa dividing the auricles 
and ventricles are wholly wanting and a bilocular heart results; or the 
auricular septum alone is absent, when the organ is trilocular. More 



DISEASES OF THE CIRCULATORY SYSTEM 469 

commonly than these conditions, the organ is completely reversed, 
lying on the right side of the body and having the blood-vessels entering 
it and leaving it reversed, so that the general venous blood enters the 
left auricle, the pulmonary blood the right auricle, while the aorta 
springs from the right ventricle and the pulmonary artery from the 
left. This condition is spoken of as dextrocardia. The abdominal vis- 
cera may be reversed at the same time, the liver being on the left and 
the spleen on the right side (situs inversus). Other abnormalities in 
the arrangement and origin of the great blood-vessels, such as an un- 
divided truncus arteriosus, are rare. 

Stenosis and atresia of the pulmonary artery result from abnormal 
situation of the septum which divides the truncus. Complete atresia 
is very rare. Stenosis is one of the commonest developmental defects of 
the heart, and in some cases is due to fetal myocarditis about the orifice. 
It may involve the root, the conus, or the trunk of the vessel. The 
septum of the ventricles is usually defective and the foramen ovale re- 
mains patulous. When the stenosis is considerable the pulmonary cir- 
culation is often maintained by the persistence of the ductus arteriosus 
botalli, and the right ventricle is greatly hypertrophied. 

Stenosis and atresia of the aorta are less frequent than the same 
conditions affecting the pulmonary artery. They arise from the same 
cause, and are usually accompanied by the same defects of the septa 
and patency of the ductus arteriosus. Stenosis of the trunk of the 
aorta at the isthmus — i. e., at a point between the left subclavian artery 
and the mouth of the ductus arteriosus — is not infrequent in moderate 
degree. More rarely there may be almost complete atresia, or the aorta 
may be entirely wanting at this point. The circulation is maintained 
by collateral anastomosis of the branches of the subclavian with the 
descending aorta. In all of these cases hypertrophy of the left ventricle 
is usually present. 

Defects of the ventricular septum may be unaccompanied by other 
abnormalities; but, as a rule, they are of secondary importance, occur- 
ring in cases of abnormality of the pulmonary artery or aorta. The 
septum may be completely wanting or there may be partial defects, 
these latter usually lying anteriorly and above, in what is known as the 
membranous portion or the undefended space. 

Defects of the auricular septum are comparatively rare, but a 
patulous condition of the foramen ovale is one of the most frequent of 
congenital affections of the heart. It is due to the failure of the valve 
of the foramen to unite at the edges, as normally occurs some time 
after birth. Slit-like openings are seen very frequently in postmortem 
examinations, while more decided patency is occasionally observed 
without other cardiac abnormalities. This is especially likely to occur 
when congenital atelectasis or some other pulmonary affection causes 
continuance of high blood-pressure in the right heart after birth. 

Stenosis and atresia of the auriculoventricular orifices are rare 
congenital conditions, and in the former fetal endocarditis doubtless 
plays an important part. When there is complete atresia the auricular 



470 A TEXT-BOOK OF PATHOLOGY 

septum must remain widely open, and the septum of the ventricle is 
usually deficient and the ductus botalli patulous. 

Patulous Ductus Botalli. — This condition is frequent in cases of 
stenosis of either the aorta or pulmonary artery, and serves to convey 
the blood from the patulous artery into that which is obstructed. Like . 
the patulous foramen ovale, it may occur as an independent condition 
resulting from congenital atelectasis of the lung which leads to the 
continuance of the fetal conditions of circulation. 

Valvular Defects. — Not rarely there may be but two semilunar 
valves at the aortic or pulmonary orifice, and, on the other hand, four 
may be observed, the latter being a relatively common condition. 
Similar numerical abnormalities occur at the auriculoventricular valves. 
Abnormal length or shortness of the leaflets may also be observed, or 
the segments may be united, forming a complete ring. The latter con- 
dition must not be mistaken for the agglutination of endocarditis. The 
leaflets may be fenestrated. 




Fig. 190. — Congenital cardiac dis- Fig. 191. — Clubbing of the fingers in congeni- 
ease, showing peculiar thickness of tal cardiac disease; from same case as Fig. 190 
lips and nose (Eichhorst). (Eichhorst). 



Pathological Physiology. — Congenital heart diseases occasion 
serious disturbances of the circulation, leading to overfilling of the 
venous channels and often abnormal mixture of the arterial and venous 
blood. In consequence of these conditions blueness or cyanosis is a 
common symptom, and the terms congenital cyanosis and morbus cceruleics 
are applied. The imperfect oxidation of the blood doubtless causes 
profound effects, but these have not as yet received accurate study. 
The imperfect circulation causes certain changes in the tissues, notable 
among which are thickness of the lips and nose, giving rise to a peculiar 
facial expression (Fig. 190) and "clubbing" of the finger ends (Fig. 
191). The blood in congenital cyanosis often contains an excess of red 
blood-corpuscles. (See Polycythemia.) 



DISEASES OF THE CIRCULATORY SYSTEM 



471 



CIRCULATORY DISTURBANCES 

Thrombosis of the cavities of the heart results from the causes 
which induce thrombosis elsewhere in the circulatory system. These 
are, mainly, slowing of the current of blood, some roughness or disease of 
the endocardial lining, and diseased conditions of the blood itself, which 
render it more liable to coagulation. Slowing of the circulation is the 
most frequent cause of intracardiac thrombosis, and leads to the forma- 
tion of the clots found postmortem in cases of gradual death. If the cir- 
culation has been slow for a considerable length of time, there may be 
found more or less grayish or white thrombi in the appendages of the 
auricles or in the ventricles between the muscular trabecular, especially 
near the apex. The formation of these is explained by the gradual 
slowing of the current of blood, which leads to the deposit of the 
leukocytes and blood-plaques upon the endocardium and the deposi- 
tion of fibrin. The color may be almost completely white; but if 
the current is almost stagnated, admixture of red corpuscles occurs 
and pinkish or quite red clots (currant-jelly clots) are formed. Of this 
latter sort are the thrombi formed in the heart during the agonal period 
and postmortem. They are further distinguished from the thrombi 
formed intra vitam by the fact that they are not closely attached to the 
endocardium and between the trabecular muscles. 

. Among the diseases in which the circulation is prone to be sluggish, 
and which are frequently accompanied by cardiac thrombosis, pneu- 
monia, tuberculosis of the lungs, the asthenic 
fevers, and diseases of the muscle of the heart 
may be named. Dilatation of the chambers 
of the heart and cardiac aneurysm lead to 
thrombosis by their effect upon the rapidity 
of the circulation either in the general heart- 
cavity in the first, or in the aneurysmal dila- 
tation in the second. Among the endocardial 
lesions which occasion thrombosis the most 
important is acute endocarditis. In this 
condition there is habitually deposited upon 
the affected part of the valves or mural endo- 
cardium a capping of fibrin deposited from 
the blood passing over the diseased area. 
In chronic endocarditis, especially when 
there are irregular calcareous deposits ren- 
dering the surface rough and uneven, con- 
siderable thrombotic deposit may occur. 

Pathological Anatomy. — Cardiac thrombi, formed some time before 
death, usually appear as deposits upon the heart wall of a yellowish or 
whitish color and rather firmly attached between the muscular trabec- 
ulse. Occasionally they have a stratified appearance, due to the fact 
that the circulation varied in rapidity during the formation of the 
thrombi. Secondary changes are not rare, the most striking being 
softening of the fibrinous mass in places, with the formation of cyst-like 




Fig. 192. — Thrombosis in 
cardiac chambers, showing cyst- 
like structure (Orth). 



472 



A TEXT-BOOK OF PATHOLOGY 



cavities varying in size from a split pea to a cherry (Fig. 192). Some- 
times thrombi project from the endocardial surface in a polypoid form, 
and these may present the appearance of fibroid tumors. A curious form 
occurs in the auricles, the thrombus presenting itself as a round mass 
attached to the endocardium by fine pedicles or lying entirely free 
(ball-thrombi, globular thrombi). 

Lesions in Other Organs. — Thrombosis of the heart may occasion 
serious disturbance of the circulation by weakening the heart muscle or 
by obstructing the valvular orifices. The latter is especially common in 
the case of the globular thrombi or the polypoid thrombi of the auricles. 
Passive congestion of the various organs and the secondary changes due 
to this condition follow. Thrombosis may lead to another and more 
serious danger, that of embolism. When portions of the thrombus are 
broken off they are carried into the circulation and lodge in the small 
arteries of the spleen, the kidney, the brain, the lungs, or elsewhere, 
causing infarctions, or, in case micro-organisms be present in the original 
thrombus, metastatic abscesses and pyemia. 

Thrombosis and Embolism of the Coronary Artery. — The 
former condition is much the more common, as the coronary arteries 
are frequently the seat of advanced atheromatous narrowing and rough- 
ening, which predispose strongly to thrombosis; and, on the other hand, 
the mouths of the coronary arteries are so placed that emboli are unlikely 
to enter. The lodgment of an embolus seriously compromises the heart's 
action, as has been shown experimentally in animals, and marked 
pathological change is, therefore, unlikely to occur before death ensues. 
When a partially obstructing embolus lodges or a thrombus is formed 
there results almost complete anemia of the area supplied by the artery 
affected, and, in consequence, an anemic infarct. The muscle-fibers of 
the affected area become hyaline or granular, and do not take the stain 
when subjected to ordinary histological examination. To the naked eye 
the diseased portion presents itself as a white, and later as a yellowish, 
area of softening, and the condition is spoken of as myomalacia cordis. 
It is found most frequently in the anterior or posterior wall of the left 
ventricle, near the apex, from the fact that the descending branch of the 
left coronary artery is the most commonly occluded vessel. Next in 
frequency to these points the anterior portion of the septum is found to 
be affected. Small areas may heal by absorption of the degenerated 
tissue, and by infiltration and proliferation of connective tissue. In 
this manner a scar is formed which may remain, or may subsequently 
lead to aneurysmal dilatation. On the other hand, rupture of the heart 
may be occasioned either with or without the formation of an acute 
aneurysmal dilatation at the degenerated area. 

DISEASES OF THE ENDOCARDIUM 

The endocardium, both mural and valvular, is subject to edema 
and hemorrhage either independently or as forerunners of inflamma- 
tion. Hematomata have been seen in the valves. Fatty, mucoid, 
hyaline, amyloid, and calcareous changes have been seen. 



DISEASES OF THE CIRCULATORY SYSTEM 



473 



INFLAMMATION 

Inflammation of the endocardium, or endocarditis, may be acute or 
chronic; the latter is in most cases merely a continuation of the former. 

Acute endocarditis affects the endocardium of the valves in the 
great majority of cases, but it is sometimes found in the endocardium 
of the cavities of the heart, when it is spoken of as mural endocarditis. 

Etiology. — Endocarditis is practically always a secondary process, 
and is in nearly all, if not all, cases due to the action of micro-organisms. 
Cold and traumatism, upon which the older writers insisted as causal 
factors, act merely as predisposing causes. Endocarditis occurs most 
frequently in association with acute articular rheumatism. Next to 
this cause, scarlet fever, pneumonia, and various forms of sepsis are 
most important, bvit in any case of suppurative or infectious disease 
endocarditis is a possible complication. Even the seemingly mild in- 
fections like tonsillitis may occasion endocarditis. It occurs at times 
also in Bright's disease and in conditions of great malnutrition, such as 
carcinoma and certain nervous affections. These cases have been cited 
as opposing the view that endocarditis is always infectious and due to 
micro-organisms. It may be that toxic substances resulting from im- 
proper metabolism act upon the endocardium as do micro-organisms, 
or that portions of the endocardium suffer degeneration as a result of 
depressed nutrition, but it is more probable that terminal or intercur- 
rent infection from some hidden source may occur in these chronic dis- 
eases, with resulting endocarditis. 

As to the micro-organisms themselves, the most important are the 
Staphylococcus pyogenes aureus, the Streptococcus pyogenes, and the 
Diplococcus pneumonia?. A special form of streptococcus distinguished 
by certain rather marked cultural features, the Streptococcus viridans, has 
in recent years been found especially frequent in certain cases of sub- 
acute endocarditis or recurrent endocarditis. There are many forms 
which have been less frequently detected. Among those reported are 
the Staphylococcus pyogenes albus, the Micrococcus endocarditidis capsu- 
latus and rugatus, the Bacillus endocarditidis griseus and capsidatus, B. 
pyogenes foetidus, B. coli communis, the B. diphtheria?, the B. aerogenes 
capsulatus (Welch), or the bacillus of Achalme, and the bacillus of ty- 
phoid fever. The tubercle bacillus has been found in a few cases, but it 
is generally believed that its presence is explained as a secondary deposit 
rather than as the cause of the endocarditis. The gonococcus has been 
found capable of causing endocarditis. 

The bacteria causing the valvular inflammation settle upon the endo- 
thelium from the blood-stream in all probability, but an infection through 
the base of the valve cannot be entirely excluded. When, by reason of 
toxins circulating in the blood, or forceful impact of the leaflets, due to 
overaction of the heart, or disturbed lymph-supply of the valve stalk, 
the endothelium swells, it forms a favorable settling place for bacteria 
passing over the valve in the blood-stream. When the bacteria have 
become attached they are taken up by the phagocyte power of the 



474 



A TEXT-BOOK OF PATHOLOGY 



endothelium. Over such a section of turgid endocardium strands of 
coagulum may appear; this adds another factor favoring bacterial attrac- 
tion by showing the current at that point. 

In all cases of general infection there is a myocarditis and, as the 
blood- and lymph-supply of the valves are scanty, edematous swelling of 
the free part of the leaflet may arise. From a lesion in the muscle near 
a valve base it is possible that bacteria may spread into the valve stalk. 

Valves are not supplied with blood-vessels, but it has been suggested 
that mild inflammations in early life leave some vascularized scar tissue 
in which capillaries may serve as avenues to the distal end of the valves, 
where lesions will occur upon a subsequent infection. 

Pathological Anatomy. — It is customary to distinguish two varie- 
ties: a simple or verrucose, or benign endocarditis; and an ulcerative, 
septic, mycotic, diphtheritic, or malignant form; but it seems unnecessary 
at the present time to maintain strictly such a distinction. The cases 



Fig. 193. — Section through a segment of the aortic valve and adjacent parts of the aorta 
and heart, showing vegetations on the aortic valve (magnified): b, Aortic valve segment; 
c, c, vegetations; /', calcareous particles in the base of the aortic valve (Bramwell). 



vary in anatomical appearance and in malignancy, but there is no essen- 
tial difference and no sharp dividing line. 

The most common seats, in order of. frequency, are the mitral valve, 
the aortic valve, the pulmonary valve, and the endocardium of the 
left ventricle, the left auricle, and the right ventricle. The part of the 
valve first involved is a line running across the leaflet at about a dis- 
tance of 2 mm. from the free edge. It is along this line that the valves 
impinge in closing, and it is probable that the mechanical injury sus- 
tained predisposes to endocarditis. In the cavities the lesions are fre- 
quently found upon the chordae tendineae, and of the parts of the mural 
endocardium proper most apt to be affected may be mentioned the por- 
tion of the left ventricle near to the septum and the aortic valves, and 
the endocardium of the left auricle on the posterior and outer wall above 
the posterior mitral leaflet. 

The first appearance of endocarditis is that of an area of opacity or 
slight roughness extending in a line across the valve or involving the 
endocardium elsewhere. Later, small nodular elevations, not unlike 




DISEASES OF THE CIRCULATORY SYSTEM 



475 



a row of small beads, may form; and finally there is a distinct, irregular, 
and wart-like fibrinous elevation (Fig. 193). To cases of this character 
the name verrucose endocarditis (Fig. 194) has been given; or, from the 
usually benign character, the name simple endocarditis; or, from its 
most frequent cause, rheumatic endocarditis. In other cases the mass of 
fibrinous deposit is more abundant and more irregular, while in still others 
the deposit of fibrin does not take place, or, if so, is soon detached, while 
necrotic changes occur in the endocardium, leading to the formation of 
irregular ulcers. Secondary deposits of fibrin may cover an ulcer after its 
formation, or its edges may be heaped with fibrin; and not rarely the 
active necrotic process in the endocardium is not visible until the fibrin- 
ous coating, which is usually considerable in such cases, is removed. 




Fig. 194. — Acute vegetative (verrucose) endocarditis. 

These forms of endocarditis are those that have been termed malignant, 
diphtheritic, septic, mycotic, or ulcerative. They are especially frequent 
after puerperal sepsis or other septic diseases and in pneumonia, but 
there is no well-established dividing line between the benign cases and 
the severe cases, either in etiology, in morbid anatomy, or in the clinical 
course and termination, so that we prefer to regard them as varying 
■ grades of the same general process. 

Microscopically, the endocardium beneath the coat of fibrin shows 
desquamation of the endothelial cells, with frequently some hyaline 
degeneration or coagulation necrosis. Below this there are round-cell 
infiltration and, as the process continues, proliferation of fibroblastic 
cells. The fibrinous covering of the valve itself consists of flakes or 



476 



A TEXT-BOOK OF PATHOLOGY 



granular masses, or a fibrillar network. By the proper staining methods 
masses of bacteria may frequently be demonstrated in the superficial 
layers of the endocardium, in the fibrinous deposit, and usually at the 
bases of the leaflets or in the muscle. 

The simple differs from the malignant forms of endocarditis merely 
in the lesser activity of the necrotic changes in the endothelium and 
the greater prominence of reparative processes (round-cell infiltration, 
proliferation of connective tissue). 

Associated with endocarditis will always be found some degree of 
myocarditis. The myocarditis is usually degenerative, but in the severe 
septic cases is infiltrative and necrotizing. Such myocarditides are 
almost always replaced by cicatrization, except in rheumatic myo- 
carditis (q. v.). 

Results. — Simple endocarditis may be healed by the gradual ab- 
sorption or breaking off of the fibrinous deposit and its dissemination 




Fig. 195. — Aneurysm of the mitral valve, with rupture of the valve-cusp, seen from 
the auricular surface: a, Wall of left auricle; b, anterior segment of the mitral valve, the 
chordae tendinese have been cut short; c, aneurysm with triangular opening (Bramwell). 

in the circulation, with coincident thickening of the endocardium at 
the point of disease by the formation of fibroblastic cells and sclerotic 
connective tissue. When the process is very limited, and especially 
when the mural endocardium is affected, merely a white spot of thick- 
ening on the endocardium results. When the process is deep there may 
be decided distortion by contraction of the new-formed connective 
tissue. When the deposit of fibrin is large it frequently undergoes cal- 
cification, and remains as an irregular, calcareous mass attached to the 
valve. In the severer or malignant cases destruction of an entire valve 
or of one of the chordae tendinese may occur. When one of the layers of 
the valve alone is penetrated acute valvular aneurysm may be formed 
by a pouching of the other layer of the valve (Fig. 195). 

Mural endocarditis of malignant type may lead to myocarditis 



DISEASES OF THE CIRCULATORY SYSTEM 



477 



of a purulent character, and may even penetrate to the pericardium and 
set up a purulent pericarditis. 

Lesions in Other Organs. — The most serious danger of endocarditis 
is embolism. Small fragments of the fibrinous deposits are liable to be 
carried off into the peripheral circulation, and in ulcerative cases frag- 
ments of the valves themselves may be so conveyed. They are prone 
to lodge in the arteries of the spleen, kidneys, and brain, forming hemor- 
rhagic infarcts or metastatic abscesses, according to the non-infective 
or infective character of the embolus. 

Subacute or chronic malignant or recurrent endocarditis is 
that form in which the pathological change in the valve is not of a 
rapidly progressive nature, but is often sluggish or chronic in its patho- 
logical and clinical behavior. The term "recurrent" has been used to 
indicate that cases of old valvular lesions are especially prone to this 
type of reinfection. There is commonly a bacteremia, the most com- 
mon organism found being a streptococcus similar to both the pyogenic 
streptococcus and the pneumococcus, called the Streptococcus viridans. 
We have discussed the nature of the infection under the general sub- 
ject of remittent infections; the reason for the persistence of the organ- 
ism in the body for so long a time will be found by consulting the text 
upon fixed or fast bacterial strains. The pathological lesions are those 
of low-grade vegetative endocarditis, with the evidences of continued 
congestion of the lymphatic tissues and bone-marrow. Nephritis may 
arise. The termination may be gradual exhaustion, an acute exacer- 
bation and death, or transition to a cicatrizing endocarditis. 

Chronic endocarditis usually affects the valves of the heart and 
leads to the distortion of the valves constituting chronic valvular heart 
disease. Clinically, there are signs of disturbances, and eventually 
more or less complete failure of the circulation. 

Etiology. — Chronic endocarditis may be merely the continuation 
of acute endocarditis, or it may occur as an insidious process, chronic 
from the outset. In the former group of cases the causes are, of course, 
those of acute endocarditis, and it is particularly the rheumatic form 
that is likely to pass on to a chronic condition. The severer grades of 
acute endocarditis, or those commonly spoken of as malignant endo- 
carditis, are usually fatal, though occasionally they may terminate by 
reparative overgrowth of fibrous tissue. The group of cases in which 
the disease is chronic from the start has much in common with arterio- 
sclerosis and atheroma, as far as etiology is concerned. They may be 
toxic in their origin. These cases occur more frequently in persons of 
advanced years and in those whose occupation has been laborious. 
Chronic alcoholism, gout, lead-poisoning, syphilis, and diabetes are 
among the recognized causes. Not rarely the endocardial disease is 
secondary to the arteriosclerosis, and it may be directly due to it, 
resulting from the constant elevation of blood-pressure due to that 
disease. Laborious occupations act in a similar manner. 

Pathological Anatomy. — In brief, the changes that occur in the 
endocardium are overgrowth of fibrous tissue, causing thickening with 



478 



A TEXT-BOOK OF PATHOLOGY 



subsequent contraction and distortion of the valves. The chordae 
tendineee are frequently involved and become converted into sclerotic 
cords of a whitish color, and less frequently white elevations are seen 
upon the mural endocardium. 

Microscopically, there are found the characteristic appearances 
of new-formed connective tissue, with occasionally, in the earlier states, 
the appearances of granulation tissue. New-formed blood-vessels may 
be found within this tissue, though frequently these are degenerated 
(hyaline and obliterated). Subsequently other degenerations take 
place. The area of thickening becomes more translucent and hyaline, 
then opaque and soft; coagulation necrosis and fatty degeneration take 
place, and there may thus be formed beneath the endocardial surface a 
lesion somewhat resembling a minute abscess. This may rupture upon 
the endocardial surface, forming a so-called atheromatous ulcer, upon 
which fibrinous deposits may collect; or it may be slowly inspissated 
and converted into a calcareous patch. In cases in which acute endo- 
carditis with thrombotic deposits passes into chronic endocarditis the 
fibrinous masses of the surface may be rendered calcareous at the same 
time that the sclerotic processes are taking place in the valve. Sub- 
sequently the same degenerative changes and calcification may occur 
in the tissue of the valve itself as are seen in the atheromatous form 
of the disease. In the late stages it is often quite impossible to deter- 
mine whether the case began as an acute endocarditis, or whether it was 
chronic from the first. 

The segments of the valves are frequently greatly shortened and 
rounded, so that they become mere stumps, or they may be curled 
upon themselves or drawn back and firmly adherent to the wall of the 
aorta, pulmonary artery, or the ventricular cavity. The individual 
segments may be agglutinated and united as a ring or diaphragm pro- 
jecting from the valvular insertion. 

The valvular function is interfered with in two ways : first, obstruc- 
tion may be offered to the outflow of blood by the rigid projecting valves 
and contracted orifice, a condition to which the term stenosis is applied; 
or, on the other hand, the valves may be so distorted, shortened, or 
drawn backward that they are no longer able to close, and insufficiency 
results. The semilunar valves are particularly prone to be shortened, 
thickened, and recurved, and insufficiency is, therefore, most likely to 
occur. The mitral valve is frequently thickened and converted into a 
funnel-like formation by agglutination of the edges of the anterior with 
those of the posterior segment. There may thus be merely a slit-like 
orifice (button-hole mitral), which occasions great obstruction to the 
outflow of blood from the auricle. Somewhat similar changes are met 
with at the tricuspid valve. The pulmonary valve is rarely affected 
in later life, but is sometimes the seat of fetal endocarditis, leading to 
permanent changes. 

Resulting Changes in the Heart. — The valvular defects can be 
overcome in only one way — by increase of the power of the heart 
muscle. Hypertrophy is, therefore, the natural result. This affects 



DISEASES OF THE CIRCULATORY SYSTEM 



479 



first the cavity upon which excessive work falls as the result of the 
regurgitation of blood in cases of insufficiency, or as the result of the 
excessive strain placed upon the heart wall to force the blood through 
the narrowed orifice in stenosis. The amount of hypertrophy varies 
with the condition of the general health of the individual and with the 
seriousness of the heart lesion itself. When the general health is good 
there is apt to be commensurately adequate hypertrophy, and when the 
lesion is not of sufficient gravity to interfere with the circulation in the 
coronary arteries, and the heart is, therefore, constantly supplied with a 
sufficiency of blood, hypertrophy is well maintained. Eventually, as 
the result of continued overwork and of continuously increasing em- 
barrassment of the circulation or of intercurrent diseases, the heart 
muscle suffers fatty or fibroid degeneration, the cavities dilate, and the 
circulation fails. 

Changes in Other Organs. — The passive congestions resulting from 
failure of the muscle of the heart are often extreme, and may lead to 
profound changes in various organs, notably the lungs, liver, and 
kidneys. These are discussed in the appropriate sections. Embolism 
is a not infrequent accident in chronic endocarditis, the emboli being 
parts of the valvular deposits or parts of thrombi in the cavities of the 
heart. 

Pathological Physiology. — Endocarditis, acute and chronic, leads to 
various disturbances of the circulation and of the general health. In 
acute endocarditis the lesions may become the center of dissemination 
of infectious material, and the disease may run its course with all the 
manifestations of an obscure septicemia. This is particularly true of the 
cases usually designated as malignant. Serious disturbance of the 
heart action occurring in acute cases is sometimes difficult to explain. 
The lesions upon the valves may be seemingly very insignificant, and 
yet the heart may be very irregular in action and exceedingly weak. 
In part this may be reflex and in part it is probably the result of 
associated disease of the myocardium. Some investigations, made 
according to modern methods, have shown the heart muscle impli- 
cated more often than has been suspected. Acute myocarditis and 
diseases of the blood-vessels of the myocardium (thrombosis) have 
been discovered. 

Chronic endocarditis (valvular disease) occasions more or less pro- 
found mechanical disorders of the circulation. The severity of these 
depend upon the condition of the heart muscle more than upon the 
severity of the valvular lesion. There is always a tendency to com- 
pensatory hypertrophy of the heart muscle, and for a time this may 
suffice to avert serious disturbances; but with hypertrophy there is 
always some degenerative change (fibrous myocarditis and, later, fatty 
degeneration), as a result of which the cardiac power eventually fails, and 
symptoms of venous congestion develop. The degree of hypertrophy 
and of degeneration depends upon the nature and severity of the val- 
vular lesion, upon the age and general condition of the individual, and 
upon associated local conditions, such as disease of the coronary artery. 



480 



A TEXT-BOOK OF PATHOLOGY 



When compensation fails the various organs of the body suffer con- 
gestion. The lungs are first affected in disease of the left heart (mitral 
and aortic disease). The capillaries of the pulmonary alveoli become 
overfull, and encroach upon the lumen of the alveoli, or by elongation 
stretch the alveolar walls and render them inelastic. In either case 
proper respiration is prevented — a condition which is further aided by 
the retarded pulmonary circulation. As a result of these conditions, 
dyspnea (cardiac asthma), cough, and expectoration develop. In ex- 
treme cases edematous exudation takes place, and in long-continued 
cases cyanotic induration of the lung occurs. In such instances there 
may be continuous cough and respiratory insufficiency. 

When the right heart fails, the liver, spleen, gastro-intestinal mucosa, 
the kidneys, and the peripheral circulation suffer congestion. The liver 
may become greatly engorged, and in certain cases (tricuspid regurgita- 
tion) actually pulsates with each ventricular systole. The swollen liver 
cells and the engorged vessels cause obstruction of the biliary capil- 
laries, and consequently produce jaundice. To some extent this may be 
due to associated congestion of the biliary channels. Congestion of the 
gastro-intestinal mucosa may occasion various forms of gastric or in- 
testinal derangement. 

Metabolic disturbances of various sorts may occur in consequence 
of the imperfect circulation. The respiratory exchange of gases, in some 
cases at least, is reduced, though the degree of cyanosis cannot be taken 
as an index of the reduced oxidation. In man cyanosis is dependent 
upon stagnation of circulation rather than reduced oxidation. The 
products of metabolism excreted in the urine may indicate the reduc- 
tion in oxygen in the tissues. The metabolic consumption of the pro- 
teins of the body seems to be increased, but the explanation of this fact 
has not yet been satisfactorily determined. Some regard it as a con- 
sequence of molecular necrosis due to insufficiency of the supply of oxy- 
gen. The excretion of nitrogenous elements may, however, be reduced 
when transudates are forming. This is due to the storing up of meta- 
bolic products in the transudates. The urine may present albumin as a 
result of chronic congestion and secondary renal disease; the hepatic 
functions are disturbed by congestion and jaundice may result; and in 
the more severe instances hydrobilinuria occurs. The condition of the 
blood is of special interest. During periods of failing compensation the 
concentration of the blood is increased or normal, and the number of 
blood-corpuscles may be excessive. In part, at least, these conditions 
are explained by the assumption that the corpuscles are retained in 
the peripheral parts of the circulation in greater measure than the fluid 
elements (see Polycythemia). When the cardiac compensation is well 
maintained some anemia may be apparent, especially in cases of aortic 
disease. 

Disturbance of the rate or rhythm of the heart is not infrequent. 
The rate is usually more rapid, but in aortic stenosis it may be slow. 
This is in effect a conservative process, as it enables the ventricle to dis- 
charge its contents through the narrowed orifice. Arrhythmia is gener- 



DISEASES OF THE CIRCULATORY SYSTEM 



481 



ally proportioned to the grade of degeneration of the muscle of the heart, 
and is especially marked in cases in which the walls of the auricles are 
involved. The attempt to connect disorders of rhythm with disease of 
the intracardiac nervous mechanism has thus far failed of demonstration. 
On the other hand, the relation of myocardial disease to arrhythmias 
has become increasingly evident. Increased irritability of the heart 
muscle in certain stages of myocardial disease readily explains some of the 
cases of extrasystolie irregularity. Lesions of the bundle of His may 
occasion partial or complete dissociation of the auricular and ventricular 
contractions (partial or complete "heart-block"). Various other types 
of arhythmia may also be explained by myocardial disease. 

Myocardium 
circulatory disturbances 

Anemia of the heart muscle may be part of a general anemia. It 
may occur in cases of narrowing or obstruction of the coronary arteries, 
and it may be the result of the pressure of pericardial effusions. When 
long continued it leads to fatty degeneration of the heart, but is itself 
of little consequence. 

Hyperemia of the heart muscle may occur Avhen there is obstruction 
to the return of the blood to the right heart through its venous channels. 
It may be part of a general hyperemia in a failing compensation of valvu- 
lar or muscular diseases of the heart. The heart muscle assumes a dark- 
red color, and the veins are seen under the epicardium as dilated bluish 
vessels. 

Hemorrhages in the heart muscle may result from obstruction of the 
coronary arteries, when the hemorrhage assumes the form of an infarct. 
There may also be hemorrhages in cases of intense myocarditis or sur- 
rounding abscesses of the heart muscle, and finally points or streaks of 
hemorrhagic infiltration may be seen between the muscle-fibers in per- 
sons who have died from some form of hemorrhagic diathesis, from 
sepsis, or from various intoxicants. 

DEGENERATIONS 

Parenchymatous degeneration, or cloudy swelling of the heart, 
was designated by Virchow as parenchymatous myocarditis. It is es- 
sentially a degenerative process and should be so described, though it 
forms a not inconsiderable part of the pathological changes occurring in 
the heart in acute myocarditis. 

Etiology. — The immediate cause is infection. It is met with in the 
course of diphtheria, typhoid fever, scarlet fever, rheumatism, and 
other infections. It may be that elevation of the temperature alone 
suffices to bring it about, and in these cases no doubt abnormal sub- 
stances resulting from disordered metabolism are the direct toxic 
agents, but, as a rule, it is the specific toxin of the infections that occa- 

31 



482 



A TEXT-BOOK OF PATHOLOGY 



sions the myocardial disease. Localized parenchymatous degeneration 
may be found in the heart-fibers adjacent to areas of endocarditis or 
pericarditis, and doubtless the same etiological factors are at work in this 
as in more generalized instances. 

Pathological Anatomy. — The changes are more marked in the left 
ventricle than elsewhere, though any part of the heart may be affected. 
As a rule, parenchymatous degeneration occurs as a diffuse process, but 
there may be only limited areas here and there. The myocardium be- 
comes pale in color; it is softer than normal, the heart walls are usually 
flabby, and the cavities somewhat dilated. Microscopically, the fibers 
are found to be filled with fine granules of albuminoid nature, which 
may completely obscure the striations and even the nuclei, but which 
may be cleared up by the addition of acetic acid. Multiplication of the 
nuclei and round-cell infiltration of the intermuscular connective tissue 
may be observed, but these are inflammatory changes rather than de- 
generative, and are not, therefore, strictly a part of the disease in 
question. Parenchymatous degeneration may be complicated by a form 
of hyaline degeneration, the affected fibers becoming converted into 
cylinders of waxy appearance. When cloudy swelling persists, fatty 
degeneration is usually the terminal change. 

Amyloid infiltration results from the causes which induce amyloid 
disease in other organs. It is not infrequently found in minute areas 
here and there, but only rarely has it been seen as a widespread process 
affecting the connective tissue between the muscle-fibers and beneath 
,the endocardium and pericardium. In such cases the same wax-like 
appearance is seen as in -the liver or spleen, and the characteristic reac- 
tion with iodin may be demonstrated. 

Hyaline degeneration is sometimes associated with amyloid, and 
gives rise to a glassy or waxy transformation of the connective tissue. 
It is usually seen in small areas, but may be quite widespread. Zenker 
described a form of hyaline disease (vitreous degeneration) of the 
muscle-fibers themselves as occurring in typhoid and other infectious 
fevers, and affecting the heart muscle as well as the muscles of the 
abdominal wall. This is usually associated with parenchymatous de- 
generation and occurs in limited areas. Microscopically, there may be 
seen small hyaline masses or globular areas embedded in the muscle- 
fiber, the rest of the fiber showing the appearances of cloudy swelling. 

Fatty infiltration, or obesitas cordis, is but an increase of the 
normal condition. In the normal heart there is a certain amount of fatty 
deposit beneath the epicardium, especially in the furrows and along the 
lines of the blood-vessels. In disease this may become enormously 
increased and there may be penetration of the adipose tissue into the 
wall of the heart between the muscle-fibers, sometimes as far as the sub- 
endocardial fibrous layer. 

Etiology. — The causes are those which induce general obesity. Thus, 
it may be the consequence of a hereditary tendency or sedentary 
habits, with overeating and drinking; it is more common in advanced 
years than in early life. Very frequently it is met with in women who 



DISEASES OF THE CIRCULATORY SYSTEM 



483 



have grown stout at the menopause; sometimes, however, considerable 
deposit about the heart may occur in persons otherwise presenting no 
tendency to fatness. 

Pathological Anatomy. — The adipose tissue beneath the visceral peri- 
cardium may be slightly increased in amount, or the heart may be em- 
bedded within an enormous deposit of fat, which may involve not 
alone the epicardium, but the parietal layer and the mediastinum as 
well. On section through the heart wall, trabecular of adipose tissue 
may be seen passing through the heart's substance, and sometimes 
deposits may be seen as a uniform infiltration beneath the endocar- 
dium, or as localized deposits projecting into the heart cavity. Mi- 
croscopically, fatty infiltration presents the ordinary appearances of 
adipose cells lying between the heart muscle-fibers (Fig. 196). The 
muscle-fibers themselves are not involved ; but may become atrophic 




Fig. 196. — Fatty infiltration of the heart, from a section through the wall of the right 

auricle (Bramwell). 

from pressure, and in such instances present a more yellowish or 
brownish color than normal, and microscopically show an abundance 
of granules. In other cases pronounced fatty degeneration is seen in 
the muscle-fibers. 

Results. — Weakening of the heart muscle must necessarily result 
from the mechanical impediment imposed upon it. Circulatory dis- 
turbances are, therefore, met with, as in valvular disease or fatty de- 
generation. Occasionally rupture of the heart occurs, due to the 
atrophic condition of the muscle proper and a want of resisting power 
of the infiltrating adipose tissue. It is especially prone to occur when 
the disease is localized. 

Fatty degeneration affects the muscle-fibers themselves. 

Etiology. — Fatty degeneration results from malnutrition or from 
toxic agencies. The most frequent cause is anemia, either local or 
general. Local anemia is due to sclerosis and narrowing of the coronary 



484 



A TEXT-BOOK OF PATHOLOGY 



arteries; or it may be the consequence of improper circulation in the 
coronary vessels attending the final stages of valvular disease of the 
heart. Fatty degeneration is, therefore, a terminal condition in arterial 
sclerosis affecting the coronary vessels and in valvular disease. The 
remote or antecedent causes are those which bring about arteriosclerosis. 
We find it, therefore, in elderly persons of the male sex who have had 
syphilis, who have used alcohol excessively, or have gout or chronic 
Bright's disease. The fatty degeneration of the heart resulting from 
general anemia is most typically seen in pernicious anemia, in which the 
most extreme grades of fatty disease are sometimes witnessed. Of the 
cases which are due to toxic agents, we may distinguish those resulting 
from specific infections and those occurring in various chemical intoxica- 
tions. In the specific fevers, in which intense parenchymatous de- 
generation occurs, and among these diphtheria is most prominent, fatty 
degeneration is sometimes the terminal condition. Among the external 
poisons capable of producing the disease phosphorus and arsenic are 
important. 

Pathological Anatomy. — Fatty degeneration may be a localized or a 
diffuse process. As a rule, a considerable portion of the heart is affected, 




but only isolated fibers or groups of fibers are involved. There results 
a somewhat speckled or mottled condition (tigration), which is especi- 
ally visible beneath the endocardium. Streaks or lines of a yellowish 
or whitish color alternate with the darker portions of normal muscle. 
When the process is uniform the entire muscle assumes a yellowish hue. 
It is softer than normal, the cavities tend to dilate, and the walls may be 
considerably thinner than normal. 

Microscopically, the muscle-fibers are found to be filled with small 
granules of a dark color or with small droplets of high refractive power 
(Fig. 197). These may completely obscure the nucleus, or they may be 
arranged in groups at the poles of the nucleus. Sometimes distinct 
vacuolization of the fibers is seen, especially in cases in which fibroid 
myocarditis accompanies the fatty change. The nature of the granules 
and droplets within the fibers is well demonstrated by treating the 
section with osmic acid, when the fat-droplets become intensely black. 

Associated Conditions. — In cases of coronary sclerosis, or valvular 
heart disease with failure of compensation, fatty degeneration is rarely 



DISEASES OF THE CIRCULATORY SYSTEM 



485 



the sole pathological condition. As a rule, fibroid myocarditis accom- 
panies it, and the latter may be the more extensive and important condi- 
tion of the two. Fatty infiltration is often met with as an associated 
condition, and may be the direct cause of the degeneration by the pres- 
sure exerted upon heart muscle-fibers by the infiltrating fat. Rupture 
of the heart may occur in cases in which fatty degeneration affects local- 
ized areas, as is often the case near the apex of the heart. 

Segmentation of the Fibers. — This is an interesting condition 
occasionally observed, especially in cases in which sudden death has 
taken place. It consists in a transverse splitting of the fibers, by which 
they are converted into columns of varying length separated by trans- 
verse fissures (Fig. 198). It has been described under the name of 
etat segmentaire or myocardite segmentaire by. French writers. A con- 
siderable discussion as to its significance has arisen, some holding that 




Fig. 198. — Marked general segmentation with great diastasis of the pieces; X 120 (from 
the American Journal of the Medical Sciences) (Hektoen). 

it is a condition of clinical as well as of pathological importance; others, 
that it occurs during the death-agony or postmortem. Whether the 
latter statement be true or not, the segmentation seems to indicate an 
abnormal fragility of the fibers and in particular of the cement- 
substance, though it may not be demonstrable by our present means 
of examination. Some observers maintain that it occurs when there 
has been excessive dilatation of the heart just antemortem. This 
fragility may be due to digestive action of bacteria or bacterial prod- 
ucts, as has been suggested. Some investigations seem to indicate 
that segmentation is purely artificial, and brought about by the imper- 
fect adjustment of the .knife in cutting. 

Degeneration of the intracardiac ganglia has been noted by a num- 
ber of observers in myocarditis and in cases of angina pectoris without 
gross cardiac alteration. The changes observed are swelling or granular, 



486 



A TEXT-BOOK OF PATHOLOGY 



fatty and hyaline degeneration of the ganglion-cells, and infiltration 
with round cells and sclerotic formation between the nerve-cells. The 
importance of these changes has not been determined. 

Pathological Physiology. — The functional disorders in degenera- 
tions of the myocardium may be due to the direct injury of the fibers, or 
to disturbances of the nervous mechanism of the heart. The latter seems 
to be the case in instances in which marked cardiac irregularity, or 
arhythmia, occurs. The disease of the fibers explains the weakness of 
the heart's action; and this is especially marked in cases of fatty and 
fibroid disease in which the circulation through the coronary arteries is 
insufficient. Recent investigations have shown that fatty degeneration 
of the heart muscle in itself causes much less cardiac weakness than has 
generally been supposed. Sometimes the heart is arrested and sudden 
death occurs in cases of myocardial degeneration due to infectious fevers 
(diphtheria). This was formerly ascribed to heart-clots, but is now 
recognized as a form of sudden and complete asystole due to the myo- 
cardial disease or to associated nervous disorders, organic (in the intra- 
cardiac ganglia or in the cardiac nerves) or reflex. The disturbances of 
the general circulation in myocardial disease and their results are 
similar to those met with in valvular disease. (See also Pathological 
Physiology of Fibroid Degeneration of the Heart.) 

The result of physiological investigations has been to give greater 
importance to the integrity of the muscle-fibers than to that of 
any intracardiac nervous mechanism in the maintenance of regular 
rhythmic action of the heart. It has been found that the muscle-cells 
have the properties of stimulability, conductivity, and contractility. 
The impulse to contraction originates near the opening of the supe- 
rior vena cava, and is conducted through certain muscle-fibers (con- 
ductivity) and received by the fibers of the auricle and the ventricle 
(stimulability), which are thus made to contract (contractility) in an 
orderly fashion. If any one of the properties is disordered, arhythmia 
or altered rates of contraction result. In passing from the auricle to the 
ventricle the impulse traverses a narrow band of muscle (atrioventricu- 
lar bundle of His), the only muscular connection; and both physiological 
experiment and autopsy findings in cases of Stokes-Adams' disease have 
shown that destruction of His' bundle causes independent contraction 
of the auricles and ventricles, the former beating as frequently as 80 or 
100, the latter between 20 and 30. The term "heart-block" has been 
given to this condition by physiologists. 

INFLAMMATION 

Inflammation of the heart muscle, or myocarditis, may be either 
acute or chronic, diffuse or circumscribed. 

Acute myocarditis was designated "carditis" by the older writers, 
though the same term was applied to endocardial and pericardial in- 
flammations as well. It may be circumscribed or diffuse, the former 
appearing most frequently in the form of abscesses of the heart muscle. 



DISEASES OF THE CIRCULATORY SYSTEM 



487 



Acute circumscribed myocarditis, or abscess of the heart, may occur 
in connection with penetrating endocardial lesions or in association with 
pericarditis. More frequently the infection takes place through the 
coronary circulation, and the metastatic abscesses of the heart are but a 
part of a general pyemic disease (Fig. 199) such as occurs in puerperal 
sepsis, in osteomyelitis, and other intensely septic diseases, but par- 
ticularly in malignant endocarditis. 

Pathological Anatomy. — When the infectious emboli are large, a 
single abscess or a few abscesses result, while in cases of finely dis- 
seminated infectious particles the heart substance may be studded with 
innumerable suppurating points. These are more common in the left 
ventricle and in the anterior wall than elsewhere. At first the lesion 
may present itself as a minute, hemorrhagic, or necrotic area, but soon 
the focus softens and forms a purulent collection. In size the abscesses 
vary from the merest points to cavities the size of a cherry, and as much 




Fig. 199. — Embolic abscess of the myocardium. 



as an ounce of pus has been removed from a single cavity. Perforation 
may take place into the heart itself, and acute cardiac aneurysm or even 
rupture of the heart may ensue. On the other hand, the abscess may 
discharge into the pericardial sac, or without such rupture may set up 
purulent pericarditis. Occasionally the pus becomes inspissated and 
fibrous overgrowth causes its complete encapsulation, or finally, the 
area may be rendered calcareous. Such terminations, however, are 
rare, the patient usually perishing of the pyemic process, as a part of 
which the abscesses in the heart occur. 

In suppurative myocarditis occurring from extension in consequence 
of malignant endocarditis communicating sinuses may be established 
between the chambers of the heart. 

A non-suppurating form of interstitial myocarditis may occur, and 
Aschoff has called attention to such a process in rheumatic conditions 
associated with endocarditis. A similar lesion has been found in the 



488 



A TEXT-BOOK OF PATHOLOGY 



heart in chorea. There is a leukocytic infiltrate and local cell hyper- 
plasia, sometimes in nodular form, following the blood-vessels. There 
may be a small amount of fibrin. This lesion occurs most commonly in 
the left ventricular wall. It may be removed without leaving a trace, 
or a small fibrotic patch may remain. 

These bodies are not producible in experimental animals by injec- 
tion of the cocci which can cause endocarditis and are said to cause 
rheumatism. 

Acute diffuse myocarditis occurs in various forms of infectious 
fevers. It was first recognized in typhoid fever, but is more common 
in diphtheria and scarlet fever, and is met with in acute rheumatism, 
puerperal septicemia, and various other infections. It is most likely 
that the toxins of the infectious diseases named are the immediate 
causes, and not the specific bacteria themselves. The process may be 
entirely diffuse, but in most cases the left ventricle is more seriously in- 
volved than other parts, and often there are merely localized areas of 
myocarditis scattered about in various parts of the ventricular wall. 

Pathological Anatomy. — The affected heart muscle is soft and often 
distinctly friable. In the earlier stages there may be spots of hemor- 
rhagic infiltration, but, as a rule, the color is rather lighter than that of 
the normal organ. It may be noticeable that the bundles of fibers 
easily separate from one another. The cavities of the heart are fre- 
quently dilated, particularly the left ventricle. 

Microscopically, the important changes are diffuse infiltration of 
round cells in the connective tissue between the muscle-fibers (Fig. 
200), and proliferation of the connective tissue itself, with formation of 
rounded or spindle-shaped fibroblastic cells. There is no tendency to 

suppuration. The blood-vessels are 
usually somewhat distended with 
blood, and there may be distinct 
proliferative thickening of their 
walls. Degenerative changes of 
the muscle-fibers themselves are 
rarely, if ever, absent, and it is 
most probable that the first stage 
in the process is a toxic degenera- 
tion of the muscle-fibers, and that 
the intermuscular infiltration and 
proliferation are consequent upon 
the primary degeneration. The 
fibers become granular and opaque, the striations are indistinct; oc- 
casionally there may be vacuolization, and sometimes the segmenta- 
tion to which so much attention has been directed. Proliferation or 
swelling of the nuclei of the muscle-fibers is frequent, and the hyaline 
transformation of Zenker is sometimes observed. 

Results. — Under entirely favorable conditions acute, diffuse, and 
non-suppurative myocarditis usually terminates in complete resolu- 
tion. It is, however, quite likely that the proliferative changes noted 




Fig. 200. — Acute myocarditis, showing 
degeneration of the muscle-fibers and mass- 
ive accumulation of leukocytes. 



DISEASES OF THE CIRCULATORY SYSTEM 



489 



in the intermuscular connective tissue often advance to complete 
organization and formation of localized areas of sclerosis. Death from 
dilatation of the cavities and cardiac failure is not uncommon. 

Chronic myocarditis, or fibrous myocarditis, like the acute form, 
maybe diffuse or localized, though in this case the circumscribed form is 
the more common. 

Etiology. — It is not unlikely that many cases are consequent upon 
acute diffuse myocarditis, as has been already suggested. In such cases 
the myocarditis may be looked upon as a primary affection. It may be 
a result of infection with Spirochaeta pallida or various intoxications. 
More commonly the process is secondary, and is dependent upon pri- 
mary disease in, or disturbances in, the circulation of the coronary 
arteries. It is, therefore, very common to find areas of sclerosis in cases 
of atheroma of the coronary arteries or in valvular disease of the heart 
in which the coronary circulation has finally become deficient. In 
view of the foregoing and the fact that the condition is not accompanied 
by a continued inflammatory exudate, this condition takes a place with 
the reparative fibroses. The primary lesion is always degenerative. 
Among the remote antecedent causes are the conditions which are prone 
to occasion arteriosclerosis, such as old age, alcohol, gout, syphilis, and 
the like. The connection between the arterial disease and the resulting 
myocardial sclerosis has been the subject of considerable dispute. No 
doubt, in some instances, the circumscribed areas of fibrous overgrowth 
met with in the distribution of branches of the coronary artery repre- 
sent the scars of healed infarctions. In other cases, however, it would 
seem more likely that a slow degenerative change with gradual over- 
growth of the connective tissue occurs in consequence of the disturbed 
circulation through the damaged coronary vessels. Diffuse sclerosis may 
be associated with hypertrophy in cases of valvular disease and other 
conditions causing cardiac enlargement. Dehio has suggested that 
fibroid degeneration or myofibrosis is a conservative process designed 
to strengthen a heart wall that has become impaired by some degener- 
ation or functional weakness, just as, according to Thoma, the fibrous 
nodules in arteriosclerosis serve to strengthen parts of the arterial wall 
that have become weakened by disease of the muscularis. 

Localized myocarditis with fibroid overgrowth is very commonly 
met with at the tips of the papillary muscles in association with chronic 
endocarditis and disease of the chordae tendineee. 

Superficial myocarditis of a fibroid character may be seen beneath 
the pericardium or endocardium which has been thickened by chronic 
inflammation. 

The association of fibroid myocarditis with uterine myofibromata 
is of some practical importance. 

Pathological Anatomy. — The characteristic change is the formation 
of sclerotic areas in the muscle substance. These appear either as more 
or less irregular spots, or as streaks or lines running in the direction 
of the fibers of the heart. They are most common in the anterior 
wall of the left ventricle, near the apex, in the septum, and at the tips 



490 



A TEXT-BOOK OF PATHOLOGY 



of the papillary muscles; but the entire substance of the heart may be 
involved and thickening of the walls may result. The impediment 
offered to the muscle of the heart by the intermuscular sclerosis may 
lead to true hypertrophy. Later, there is degeneration of the fibers in 

consequence of the pressure of 
the new-formed tissue, and yel- 
lowish areas of fatty degenera- 
tion are frequently observed. 

Microscopically, the diseased 
areas are found to consist of more 
or less well-organized connective 
tissue lying between the muscle- 
fibers and pressing them far 
apart, or taking the place of 
atrophic muscle-fibers (Figs. 201 
and 202). 

Sometimes certain portions 
show the earlier stages of the 
process, round-cell infiltration 
and proliferation of the connec- 
tive tissue being the important features (Fig. 203). As a rule, however, 
the diseased areas are found in a completely organized condition. The 
muscle-fibers themselves suffer granular and fatty degeneration, and 
not infrequently distinct vacuolization is observed. 




Fig. 202. — Chronic myocarditis, showing extensive destruction of fibers. 

Results. — In cases in which a considerable area of chronic myocarditis 
has developed, as is not uncommonly observed at the apex in conse- 
quence of thrombotic or embolic obstruction of the anterior coronary 
artery, an aneurysm of the heart may result from gradual stretching of 
the fibroid area. In cases in which the process is diffuse the heart muscle 




Fig. 201. — Edge of an area of fibrous myo- 
carditis, showing replacement of the fibers by 
connective tissue (Orth). 



DISEASES OF THE CIRCULATORY SYSTEM 



491 



may at first undergo hypertrophy in consequence of the excessive labor 
imposed upon it, but eventually degeneration from pressure upon the 
fibers gains the ascendency, dilatation of the cavities ensues, and general 
failure of the circulation is the terminal result. 

It is not unusual to find diffuse arteriosclerosis and fibroid disease 
of other organs associated with chronic myocarditis. In such cases the 
antecedent cause is the arterial disease, which, in turn, may be dependent 
upon some systemic disorder. 

Pathological Physiology. — The immediate effect of chronic myo- 
carditis or fibroid degeneration of the heart is a loss of power. By 
some it has been held that the fibroid tissue is designed as a sup- 




Fig. 203. — Endomyocarditis, showing, a, thickened endocardium; b, bands of muscle- 
fibers with interstitial infiltration of round cells and proliferated connective tissue (Bram- 
well). 

port for the heart muscle weakened by other causes, such as degenera- 
tion of the muscle-fibers themselves, just as it has been claimed that 
nodules of arteriosclerosis are intended as support for areas of weak- 
ness of the muscular layers of the arterial walls. This theory is not 
generally accepted; but, on the other hand, it is certain that the pres- 
ence of fibrous tissue weakens the heart so far as its proper function 
(contractility) is concerned. For a time hypertrophy of the muscular 
elements may counterbalance the functional weakness occasioned by 
the fibroid change, but eventually the muscle fails, and this failure is 
usually hastened by fatty degeneration and atrophy of the muscle- 
fibers, which changes, in turn, are doubtless occasioned by the fibrosis, 



492 



A TEXT-BOOK OF PATHOLOGY 



especially that involving the walls of the small nutrient arteries. In the 
early stages, with adequate hypertrophy, symptoms may be wanting, 
though a strong action of the heart and an increase in its size may be 
detected. Later, progressively increasing weakness of the circulation, 
and eventually all the signs of cardiac failure develop, just as in ad- 
vanced valvular disease. Irregularity of the heart's action is much 
more pronounced than in valvular disease, and is particularly promi- 
nent when the walls of the auricles are especially involved. It has been 
ascribed to implication of the intracardiac mechanism, but no satisfac- 
tory demonstrations of this have been made. For the present it can 
only be said that the irregularity of action results from the disease of the 
muscle and the consequent disturbance of its automatic contractility 
and other functions. 

Angina Pectoris. — In many cases of fibroid heart, paroxysms of 
pain occur. These may be moderate in severity and without definite 
characters, or they may be severe and of a uniform kind. The latter 
constitute the condition called angina pectoris. This is especially 
marked and frequent in cases of fibroid heart associated with advanced 
sclerosis of the coronary arteries. The cause of the paroxysms is uncer- 
tain. The seizures may possibly be due to minute embolisms and throm- 
boses of branches of the coronary arteries, or to muscle cramp caused by 
cardiac strain under effort or excitement in cases in which the coronary 
disease prevents a sufficient supply of blood. The former explanation 
derives some support from the recognized painful seizures that attend 
arterial occlusion everywhere, and from the disseminated patches of 
sclerosis of the heart muscle in cases of fibroid heart with coronary dis- 
ease and a history of angina. These patches of sclerosis may have had 
their origin in such embolisms or thromboses as are postulated. The 
muscle-cramp theory has its best support in the analogy of anginal 
paroxysms, with the symptoms of intermittent claudication of the legs 
in cases of generalized arteriosclerosis. Neither of , these explanations, 
however, suffices for all cases. Changes in the intracardiac ganglia and 
in the fibers of different parts of the cardiac nervous mechanism have 
been described, but are of uncertain significance. 

HYPOPLASIA AND ATROPHY 

Hypoplasia of the heart is a congenital condition in which the 
heart is insufficiently developed and remains undersized throughout 
life. This condition is frequently associated with hypoplasia of the 
aorta and other large vessels, and sometimes with a similar condition 
of the generative organs. Persons presenting status lymphaticus 
and women who develop chlorosis not rarely present the conditions 
referred to. These individuals are often of delicate structure, with 
feeble or unstable circulation, and, in the case of males, of effeminate 
nature and appearance. The heart is small in size and, as a rule, 
uniformly affected in all parts. The epicardium may be somewhat 
wrinkled, and this condition, no doubt, has often led to the description 



DISEASES OF THE CIRCULATORY SYSTEM 



493 



of cases of this sort as instances of atrophy. Many cases of supposed 
hypoplasia are doubtless instances of true atrophy, the size of the heart 
being strictly proportioned to the emaciated body. 

Atrophy of the heart is usually described as occurring in two varie- 
ties, simple and brown atrophy. It is very doubtful, however, if simple 
atrophy ever occurs. Many of the cases so designated were doubtless 
hypoplasias, and other probably broAvn atrophies. 

Etiology. — Atrophy of the heart usually occurs in persons of ad- 
vanced age; but is occasionally met with in the young. It results from 
simple senility or from various cachectic or wasting diseases, such as 
tuberculosis, carcinoma, and the like. 

Pathological Anatomy. — The heart 
is small in size, sometimes weighing 
but a third or fourth of its normal 
weight. The capsule, or epicardium, 
is wrinkled, and may be somewhat 
thickened by fibrous tissue overgrowth 
or by fatty or mucoid change. The 
vessels are conspicuously tortuous 
(Fig. 204). The muscle is flabby and 
often quite dark in color. 





Fig. 204. — Atrophy of the heart, seen 
from the front (two-thirds natural size) 
(B ram well). 



Fig. 205. — Brown atrophy of the heart 
muscle. 



Microscopically, the fibers are found smaller than normal and con- 
tain excess of pigment. The latter is brownish or black, and at first 
situated at the poles of the muscle nuclei (Fig. 205). Later the whole 
fiber may be uniformly pigmented. Sometimes the muscle-fiber is 
converted into a hollow sheath, containing scattered pigment granules 
and more or less fragmented nuclei. Complete destruction of the fiber 
may lead to the apparent occurrence of pigment between the muscle- 
fibers. The pigment does not contain iron, and seems to be a deriva- 
tive of the albuminous constituents of the fibers. 

Localized atrophy of the fibers may occur around areas of disease 
of the heart muscle, such as foci of myocarditis, tubercles, gummata, 
etc. The fibers present the same appearances as those just described. 

Pathological Physiology. — Atrophy of the heart muscle does not 
often occasion striking results or symptoms, as the process is in most 



494 



A TEXT-BOOK OF PATHOLOGY 



cases commensurate with the general emaciation and decreased de- 
mand. Occasionally irregular action of the heart is noted, and sudden 
death has sometimes occurred. 

HYPERTROPHY AND DILATATION 

Hypertrophy and dilatation are usually associated and result from 
the same causes, the degree of hypertrophy or of dilatation present 
in a given case depending upon the suddenness of action or the intensity 
of the cause, and upon the state of the heart itself. A sudden strain may 
cause immediate dilatation; repeated strains of less severity cause 
hypertrophy in a well-nourished heart, or increasing dilatation in one 
the seat of myocardial weakness or degeneration. 

Etiology. — The influence of valvular diseases (q. v.) of the heart 
in developing hypertrophy has been sufficiently discussed. Various 
other causes may lead to overwork or cardiac strain, and occasion 
hypertrophy or dilatation. We may classify the causes in accordance 
with their operation upon either or upon both ventricles. 

Causes Acting on the Left Ventricle. — All forms of arterial disease, 
but especially diffuse arteriosclerosis, increase the work of the left 
Ventricle notably, and may cause marked changes in it. Aneurysms 
of the aorta, however, have surprisingly little effect. Chronic Bright's 
disease, especially the interstitial form, is a well-known cause. It prob- 
ably acts in several ways: partly by the associated arterial disease, 
partly by vascular contraction due to toxic products, and partly by the 
direct stimulation of cardiac action by the same substances. Excessive 
exercise or laborious occupations (mining, blacksmithing, etc.) may act 
upon the whole heart, but especially upon the left ventricle. 

Causes Acting on the Right Ventricle. — Diseases of the lungs and 
pleura, such as emphysema, fibroid phthisis, and pleural synechia?, 
are frequent causes of hypertrophy and dilatation of the right ventricle. 

Causes Acting on the Heart as a Whole. — General functional over- 
stimulation may cause uniform enlargement of the organ. This may 
be seen in cases of hysteria, exophthalmic goiter, and other diseases in 
which the overaction is due to nervous influences. Excessive eating 
and drinking affect the left more than the right ventricle, but influence 
both sides to some extent. Habitual excessive beer-drinking is most 
striking in its effects, and doubtless acts through the constantly recur- 
ring overdistention of the blood-vessels, as well as through the excess 
of nutriment and direct stimulus conveyed to the organ. Pericardial 
adhesions may occasion continuous overaction of both ventricles. 

Any of the causes named may occasion hypertrophy or dilatation, 
or both. The degree of hypertrophy is dependent upon the previous in- 
tegrity of the heart muscle, the state of the general health, and the 
manner of action of the cause. Sudden strains are more likely to cause 
dilatation, and pure dilatation may result if the muscle of the heart is 
degenerated. This is illustrated by cases of acute dilatation of the heart 
in the course of infectious fevers. 



DISEASES OF THE CIRCULATORY SYSTEM 



495 



Pathological Anatomy. — Four forms of enlargement of the heart 
may be distinguished: First, the walls are thickened and the cavities 
are smaller than normal; this is known as concentric hypertrophy, but 
it is likely that the decreased size of the cavities is due to postmortem 
contraction; second, hypertrophy of the walls with normal cavities is 
spoken of as simple hypertrophy; third, hypertrophy with cavities of 
increased size is known as eccentric hypertrophy, or hypertrophy with 
dilatation; and, fourth, there may be pure dilatation without hyper- 
trophy. _ In hypertrophy the muscle substance is darker than normal 
and is increased in consistency. Microscopically, the fibers are in- 
creased in thickness, and there is probably also increase in the number 
of the fibers. The nuclei of the muscle are swollen and multiply; myo- 
cardial degeneration (fibrofatty) is often associated. When dilatation 
is present the heart muscle is usually softer, more flabby, and generally 
somewhat lighter in color, due to associated degeneration. 




Fig. 206. — Hypertrophy of the left ventricle. 



The shape of the heart varies from the normal. When the left 
ventricle is hypertrophied the organ is increased in length and extends 
further to the left than normal (Fig. 206). When the right ventricle is 
hypertrophied the organ assumes a rounded shape; its apex is less sharp 
and the transverse measurement of the organ is greatly increased. The 
weight and size of the heart may increase enormously, and the term 
cor bovinwn is often highly appropriate. Weights of from 500 to 800 gm. 
are not infrequent, and may be greatly exceeded. Stokes recorded a 
case in which the weight was 1980 gm. 

Pathological Physiology and Results. — Hypertrophy is a relative 
process which serves to counterbalance the valvular or other impedi- 
ments to the circulation. Occasionally there may be excessive hyper- 
trophy, but, as a rule, it is merely sufficient to maintain the circulation 



496 



A TEXT-BOOK OF PATHOLOGY 



under ordinary conditions with less reserve power than is met with in 
health. In consequence, valvular lesions or arteriosclerosis may occasion 
no symptoms for a long time, provided the individual leads a quiet life. 
Eventually, however, when intercurrent diseases have determined 
cardiac weakness, or when the impediment to the circulation has 
advanced to an excessive degree, dilatation ensues and failure of the 
circulation is the consequence. When the left ventricle is at fault 
congestion of the pulmonary system occurs, and edema, hemorrhage 
from the lungs, or thrombosis with infarction of the lungs may take 
place. When the right ventricle fails, general systemic congestion, 
cyanosis, and dropsy are the consequence. 

Great hypertrophy, while it results from arterial disease, very fre- 
quently reacts upon the arteries and increases existing arterial disease, 
or occasions arterial disease when it has not previously existed. This 
is due to the increased force with which the blood is projected from the 
ventricular cavity and the increased distention which the arteries suffer 
in consequence. 

ANEURYSM 

This is a rare condition of the heart. It is usually found in the ante- 
rior wall of the left ventricle, near the apex, but may affect any part of 




Fig. 207. — Aneurysm of the left ventricle: the sac through which the probe was passed 
was situated posteriorly; the unopened aneurysm on the right was anterior; the heart is 
somewhat twisted out of its usual shape to show both sacs in the illustration (Sailer). 

the auricles or ventricles (Fig. 207) . Sometimes it is difficult to distinguish 
simple dilatation from aneurysm. The usual cause of aneurysm is coro- 



DISEASES OF THE CIRCULATORY SYSTEM 



497 



nary obstruction, with resulting degeneration of localized areas of the 
wall of the heart. First, there is softening (myomalacia), and this may 
occasion acute aneurysmal dilatation and even rupture of the heart. 
In other cases the degenerated area becomes fibrous and subsequently 
dilates. Acute aneurysm of the heart wall may similarly occur in cases 
of mural endocarditis. Rupture in such chronic cases is a rare termina- 
tion. 

WOUNDS AND RUPTURE OF THE HEART 

Non-penetrating and even penetrating wounds of the heart wall 
are sometimes recovered from, the injury being repaired by scar-tissue 
or fibrous myocarditis. As a rule, penetrating injuries occasion rapid 
death by hemorrhage into the pericardium. Spontaneous rupture of 
the heart may be occasionally the result of severe strain of a normal 
heart, but, as a rule, it occurs when there is myocardial disease. Myo- 
malacia cordis, fatty degeneration, malignant endocarditis, and abscess 
are the conditions most likely to occasion rupture. 

INFECTIOUS DISEASES 

Tuberculosis may occur in the form of acute miliary tuberculosis, 
affecting either the endocardium, myocardium, or pericardium; while 
caseous tubercles result from extension of tuberculous adenitis from the 
anterior or middle mediastinum. 

Syphilis is rare, but may occur in the form of gumma or of diffuse 
infiltration. In the latter case generalized fibrous myocarditis, indis- 
tinguishable in its gross appearances from non-syphilitic cases, may 
occur. Gummata may lie immediately beneath the pericardium or en- 
docardium, and after softening by degeneration may rupture on the 
surface. The degenerated areas may be unaccompanied by circum- 
ferential reaction, and may go into almost complete resolution without 
scar-tissue. On the other hand, the fatty area may have about it infil- 
trative and proliferative inflammation and other degenerations. The 
spirochetes are numerous in early stages. These areas are replaced by 
fibrous tissue whether or not they were originally associated with inflam- 
matory processes. They are probably due to colonization of spirochetes. 

Actinomycosis may involve the heart by extension from the medi- 
astinum or by embolism. ^Yhite or grayish nodules are formed, and 
subsequently degenerate. 

NEW GROWTHS AND PARASITES 

Primary tumors of the heart are extremely rare. Sarcoma, fibroma, 
lipoma, myxoma, and myoma with muscle cells comparable to the cardiac- 
cells have been met with, and usually occur in the form of wart-like 
growths projecting into the cavities beneath the endocardium. Organ- 
ized pediculated thrombi have frequently been mistaken for tumors. 

Secondary tumors are more common. Sarcomata of the medi- 
astinum may involve the pericardium, or even the heart wall, by direct 

32 



498 



A TEXT-BOOK OF PATHOLOGY 



extension, while secondary carcinomata and sarcomata may affect 
the myocardium by metastasis. In the latter instances nodular forma- 
tions are seen embedded in the heart muscle. 

Parasites. — Echinococcus cysts are occasionally seen beneath the 
endocardium or pericardium, and may rupture into the cavities of the 
heart, with resulting embolism. The cysticerci of Taenia solium and of 
T. saginata have occurred in man, but are more common in animals. 
The larval Linguatula rhinaria is a rare parasite of the heart. 

The Pericardium 

The pericardium is a membranous sac enclosing the heart and 
the root of the great blood-vessels. It is composed of a fibrous outer 
layer, and is lined within by flat endothelial cells. Normally it con- 
tains from 5 to 50 c.c. of clear serous liquid. 

Partial or complete absence of the pericardium is sometimes seen, 
especially in cases of ectopia of the heart. Occasionally diverticula are 
present congenitally. 

CIRCULATORY DISTURBANCES 

Hyperemia of the pericardium may occur in valvular heart disease 
or in cases of tumor or aneurysm causing intrathoracic pressure. 

Hemorrhages. — Extreme passive congestion with ecchymotic hemor- 
rhages is found postmortem in cases of death from asphyxia. Small 
punctate hemorrhages are also occasioned by various infectious diseases 
and by certain poisons, as phosphorus. They are also seen in pernicious 
anemia, scurvy, purpura, and other blood diseases. 

Hemopericardium is a term applied to accumulation of blood in the 
pericardial sac. It may result from rupture of the heart or of aneurysms 
of the aorta, pulmonary artery, or coronary arteries. The serous 
effusion of inflammatory conditions of the pericardium may some- 
times contain considerable blood which has escaped from the small 
blood-vessels in the inflamed tissue. This is more common in inflam- 
matory effusions of the pericardium than of other serous membranes, 
and is particularly true of tuberculous and cancerous cases. 

Hydropericardium, or dropsy of the pericardium, may occur when 
passive congestion is continued, or as a part of anasarca. Occasion- 
ally the liquid is milky {chlyous hydropericardium). 

INFLAMMATION 

Inflammation of the pericardium, or pericarditis, is the most 
important pathological process affecting this serous sac. 

Etiology. — Pericardial inflammations may be primary or secondary. 
In the former the irritants are conveyed to the pericardium through 
the blood, while in the latter the inflammation results from extension. 
Primary pericarditis occurs in association with various infectious dis- 
eases, notably acute rheumatism, scarlet fever, small-pox, influenza, and 



DISEASES OF THE CIRCULATORY SYSTEM 



499 



intense septic infections. These cases are termed "primary" because 
they are not extension processes, but hematogenic. It is also met with 
in the course of nephritis, either acute or chronic. Secondary peri- 
carditis may result from extension of inflammation from the pleura, the 
lung, the mediastinal glands, the sternum, the esophagus and stomach, 
or from the heart itself. 

In many instances, even when the pericarditis has occurred in the 
course of an infectious disease, micro-organisms are not discovered in 





Fig. 208. — Acute pericarditis (Bramwell). 

the exudate ; this may be due to the arrest of the micro-organisms in 
the pericardial tissues; staphylococci, streptococci, pneumococci, and 
tubercle bacilli have all been found. 

Pathological Anatomy. — Several varieties may be distinguished, 
though one form may merge into another. 

Fibrinous or Dry Pericarditis. — The first change noted in pericarditis 
is a dulness or lusterless condition of the surface of the membrane. 
Somewhat later distinct granulations, or a thin coating of fibrin, appear 
upon the surface, and this may increase until the deposit has a notable 



500 



A TEXT-BOOK OF PATHOLOGY 



thickness. The movements of the heart may give the latter a marked 
roughness or rugosity, and the term applied by older writers, cor villosum, 
is not inappropriate (Fig. 208). Microscopically, there is seen a deposit 
of granular or fibrillar fibrin upon the surface, while the endothelial 
cells are loosened and partly degenerated, and the subendothelial tissues 
are infiltrated with round cells. The blood-vessels are generally widely 
dilated, and punctiform hemorrhages may be observed. 

Serofibrinous Pericarditis. — The pericardial exudate rarely remains 
purely fibrinous in character. Usually there is some serous outpour- 
ing, and the sac becomes distended with more or less abundant tur- 
bid, serous liquid, in which flakes of fibrin are suspended. In such cases 
the fibrinous deposit is generally slight. Later the fluid may be reab- 
sorbed, leaving a simple fibrinous pericarditis. 

Purulent pericarditis, or pyopericardium, may begin as a fibrinous 
or serofibrinous process, or it may assume the suppurative form from the 
very start. In these latter cases the cause of the pericarditis is usually 
some intense general infection, as in puerperal pyemia and septicemia, 
or it may be a local infection, as in cases in which an esophageal or gastric 
ulceration has ruptured into the pericardium, or in which a caseous tuber- 
culous focus or purulent pleurisy has found a similar discharge. The 
pericardial sac is filled with purulent or seropurulent liquid, and the 
pericardium itself is covered with fibrinopurulent exudate. The 
superficial layers of the myocardium are frequently involved by in- 
flammatory edema, myocarditis, or fatty degeneration. 

Hemorrhagic pericarditis is met with in individuals of low vitality 
and in persons suffering from scurvy, purpura, and similar affections. 
Pericarditis accompanying tuberculosis or cancer of the pericardium is 
specially prone to assume a hemorrhagic type. Usually the exudate is 
serous, but distinctly colored with blood; sometimes it is almost com- 
pletely hemorrhagic. 

Terminations of Acute Pericarditis. — Any of the forms described 
may persist for a considerable length of time without change, but 
usually certain alterations are noted. In the fibrinous variety or in the 
serofibrinous form, after the liquid has been reabsorbed, the visceral and 
the parietal pericardium lie in contact and are agglutinated by the exu- 
date. Gradually the inflammatory processes beneath the fibrinous 
exudate extend into the fibrinous coating; connective-tissue hyperplasia 
and new formation of blood-vessels follow, and granulation tissue unites 
the adjacent layers of pericardium. At the same time the fibrinous 
exudate is reabsorbed and subsequently organization of the granulation 
tissues is completed. Fibrous adhesions binding the two layers of the 
pericardium together ensue, and at times complete obliteration of the 
sac is the consequence (Figs. 209 and 210). In cases in which the in- 
flammation is slight, or in which the layers are kept apart by persistent 
serous exudate, the areas of inflammation gradually become thickened 
by new-formed fibrous tissue, and there remain upon the surface of the 
pericardium sclerotic spots, often spoken of as "milk spots." Occa- 
sionally portions of the fibrinous exudate remain unabsorbed, and 



DISEASES OF THE CIRCULATORY SYSTEM 



501 



together with the thickened membrane itself and the adhesions suffer 
calcareous infiltration. The heart may thus be encased in calcareous 
plates of considerable thickness. An infrequent termination is the 




Fig. 209. — Adhesive pericarditis, showing fibrin deposit, with new blood-vessels extending 

upward into it (Perls). 

retention of tabs of thick fibrin, covered by connective tissue, con- 
taining considerable fluid. These give the impression of small peduncu- 
lated cysts. 



I. 



<' - tfs ■ if, a*** 1 " i 



Fig. 210. — New blood-vessels and fibroblastic cells in a beginning adhesion of the peri- 
cardial layers. 



Purulent pericarditis may terminate by discharge of the exudate 
into the esophagus, stomach, pleura, or even into the bronchi, and by 



502 



A TEXT-BOOK OF PATHOLOGY 



the subsequent adhesion of the two layers of the sac. In other cases 
gradual inspissation of the pus takes place and the cheesy residue may 
remain or eventually become calcareous. 

Associated Conditions. — While, on the one hand, pericarditis often 
follows inflammatory processes in the surrounding parts, it, on the 
other hand, not infrequently occasions disease of the adjacent structures. 
In most cases of severe acute pericarditis there is some associated 
inflammation of the mediastinal structures and of the pleura contiguous 
to the pericardium. Cases which terminate with the formation of 
fibrous adhesions within the pericardial sac usually also present me- 
diastinal and pleural adhesions with the external surface of the peri- 
cardium (pericarditis interna et externa). Myocarditis extending to a 
depth of 1 or 2 mm. is seen in nearly every case of pericarditis. In cases 
in which considerable pericardial exudate is present the heart muscle 
is pressed upon and impeded in function, so that venous congestions are 
commonly observed. Adhesive pericarditis leads to hypertrophy and, 
later, dilatation of the chambers of the heart. 

INFECTIOUS DISEASES 

Tuberculosis of the pericardium may result from the extension of 
pulmonary or pleural tuberculosis, or of tuberculous affections of the 
mediastinal glands. More rarely direct infection may occur through the 
medium of the circulation. Miliary tubercles are formed in the sub- 
serous and serous layers of the membrane, while the surface is covered 
with fibrinous exudation. The attendant pericarditis may be entirely 
fibrinous and the tubercles may be hidden from view by a thick deposit. 
In other cases there is serous, hemorrhagic, or purulent exudation, the 
latter especially in cases in which vomicae containing infective matter 
have ulcerated into the pericardial sac. Tuberculous pericarditis may 
terminate by gradual absorption of the exudate and fibrous adhesion, 
sometimes with calcareous infiltration. In other cases the necrotic and 
destructive changes characteristic of tuberculous processes elsewhere 
gain the ascendency, and the disease proves fatal by the seriousness 
of the cardiac involvement. 

Syphilis is an extremely rare condition. Certain indurative changes 
in the pericardium have, however, been met with in association with 
syphilis of the heart. 

Actinomycosis may result from extension of actinomycosis of the 
mediastinum or of the lungs. 

TUMORS AND PARASITES 

Primary tumors, such as lipoma and fibroma, are extremely rare. 
Secondary carcinoma and sarcoma are more frequent. They result from 
similar growths in neighboring structures. Hydatid cysts and cysti- 
cerci are occasionally met with. 



DISEASES OF THE CIRCULATORY SYSTEM 



503 



PNEUMOPERICARDIUM 

Pneumopericardium (air in the pericardium) may result from 
perforation of the sac in cases of fracture of the ribs or from penetration 
of foreign bodies through the esophagus into the pericardium. It also 
results from rupture of gastric or esophageal ulcers, and a certain 
amount of gaseous accumulation complicates purulent pericarditis when 
the exudate undergoes decomposition. The association of air and pus 
(pneumopyopericardium) more often results from secondary purulent 
inflammation after the development of pneumopericardium. 

The Arteries 

Anatomical Considerations. — The arteries and veins consist of 
three coats, called, respectively, the intima, or inner coat; the media, 
or middle coat; and the adrentitia, or external coat. The intima con- 
sists of a layer of endothelial lining cells, below which there is a thick 
fibrous layer and then an elastic membrane. The middle coat con- 
sists of smooth muscle- and elastic fibers, while the outer coat is 
composed of fibro-elastic tissue. Small blood-vessels, the vasa vaso- 
rum, ramify through the adventitia and outer media, but the in- 
tima and immediately subjacent media are avascular, and probably 
nourished from within the vessel. 

CONGENITAL DEFECTS 

Certain defects of distribution and of origin of the larger trunks 
have been referred to in the discussion of congenital defects of the heart. 
Very commonly there are anomalies in the arrangement of the periph- 
eral branches, but these are merely of anatomical interest. 

Hypoplasia. — A condition of importance is congenital smallness, 
or hypoplasia. This may affect the aorta and larger vessels together 
with the heart, or it may be confined to the blood-vessels, the heart 
being normal. Vascular hypoplasia has been especially met with in 
chlorotic girls, and also occurs in cases of status lymphaticus. The 
aorta is sometimes so small that it barely admits the little finger, and 
the walls are usually correspondingly decreased in thickness. Decided 
elasticity of the coats of the vessels may be observed. 

HYPERTROPHY 

This occurs when a collateral circulation is established in conse- 
quence of obstruction of an artery. Similarly, in the new formation of 
tissue the blood-vessels first formed are delicate vascular channels, which 
subsequently hypertrophy and are converted into well-developed 
arterioles. In this case there is a uniform overgrowth of each of the 
component parts of the blood-vessel, and not a mere hyperplasia of one 
or another coat. 



504 



A TEXT-BOOK OF PATHOLOGY 



ATROPHY 

This may occur in a part which is undergoing general atrophy, or 
where there is pressure and anemia of certain areas. Degeneration of 
the walls usually takes place in such cases, and the conditions are, 
therefore, more properly considered among degenerations. 

DEGENERATIONS 

Fatty Degeneration. — Any one of the coats may be affected, but 
the process is most common in the intima. Fatty degeneration is one 
of the important factors in atheroma; more rarely it occurs as an inde- 
pendent affection of the blood-vessels. In the latter case disturbances 
of circulation and toxic agencies in the blood are the immediate causes. 
Small white or yellowish spots or streaks may be seen in the endo- 
thelium, and microscopically the endothelial cells may be found granular 
or filled with fat-drops. In cases of greater severity there may be actual 
erosion of the endothelial surface. In cases in which the media is 
affected the muscle-cells undergo fatty degeneration. Fatty degenera- 
tion may occasion rupture of the blood-vessels, or calcareous infiltra- 
tion may ensue. 

Calcareous infiltration is the common termination of atheroma, 
but sometimes calcification of the intima or media, or even of the entire 
wall of the vessel, may be observed without arteriosclerosis. The 
process is most common in the intima and media, and, aside from the 
instances in which it is a part of atheroma, it may occur in consequence 
of circulatory disturbances, or as the result of bone disease, with de- 
struction of osseous tissue and surcharge of the blood with earthy 
salts. 

Hyaline degeneration is a condition the nature and uniform char- 
acter of which remain in doubt. A form of hyaline degeneration is very 
common in the hyperplastic tissue of arteriosclerosis, and is generally the 
first evidence of beginning degeneration. It is met with in small blood- 
vessels which are obstructed by thrombi, or which are subjected to de- 
structive pressure by inflammatory new growths or other causes. Not 
infrequently it is due to infectious fevers or intoxications, and in these 
cases the small arteries and the capillaries are prone to be affected. 
Hyaline degeneration of the blood-vessels is the striking feature of 
certain cylindromata (see Fig. 70) . The artery may show a uniform or 
a more nodular, firm, opaque thickening, and under the microscope the 
subendothelial tissue, the adventitia, or the entire wall of the blood- 
vessel may be found converted into vitreous substance. Rupture of the 
affected vessel is a not infrequent result. 

Amyloid infiltration commonly begins in the blood-vessels of the 
parts of the body in which this disease is found. In the kidneys the 
capillary tufts of the Malpighian bodies, and in the spleen the capil- 
laries within the follicles, are first affected. In these cases the entire 
wall of the vessel is involved, and presents the characteristic appear- 



DISEASES OP THE CIRCULATORY SYSTEM 



505 



ances of the disease. Amyloid disease is sometimes found in the intima 
of the larger blood-vessels, occurring in small linear or punctate areas, 
and scarcely to be recognized excepting by chemical tests. 

INFLAMMATION 

Inflammation of the arteries may affect the inner, the middle, or 
the outer coat, and in a strict anatomical sense the terms endarteritis, 
mesarteritis, and peri-arteritis are justified; but, as a rule, all three 
coats are more or less involved at the same time, and no practical dis- 
tinction can be drawn. There may be acute or chronic inflammation. 

Acute Arteritis 

Acute arteritis may be of two kinds: a suppurative or necrotic 
form and a productive form. 

Acute suppurative arteritis occurs in the arteries traversing areas 
of suppurative inflammation, and results from the extension of the 
suppurative process. It may also occur in consequence of the lodg- 
ment of infected emboli or as a result of infection of thrombi within 
the vessels. 

When the process extends from without, the adventitia and then 
the media are infiltrated with round cells, and in cases of some of the 
larger vessels there may be visible points or collections of pus. The 
process may extend as deeply as the intima, and may completely per- 
forate the wall of the vessel, leading to hemorrhage. The intima itself 
is not directly involved by the suppurative process from the lack of inde- 
pendent blood-supply, but the emigrated leukocytes may infiltrate it, 
and degenerative changes are common in the endothelium. Where the 
process begins by infection within, as through softened thrombi or in- 
fectious emboli, there is first necrotic or degenerative destruction of the 
intima, and subsequently infiltration of the media and adventitia 
with emigrated round cells (Fig. 211). 

A form of infectious arteritis resembling malignant endocarditis 
has been observed in association with that condition in a few instances. 
Ulcerated patches are seen in the intima of the aorta, and acute aneurys- 
mal dilatation or even perforation has been met with. 

Acute productive arteritis (also called proliferating or obliter= 
ating, according to its result) is most commonly the result of tissue 
changes surrounding the arteries, and is, therefore, constantly met with in 
diseases of organs leading to overgrowth of connective tissue. The con- 
dition is chronic rather than acute in such instances. Acute productive 
arteritis also occurs as a consequence of thrombosis, either of non-septic 
embolic origin or arising in loco, within the blood-vessels when the 
latter are not infected. The term thrombo-arteritis has been applied to 
these cases. It is by thrombo-arteritis that wounds of vessels are closed 
and the lumen of the blood-vessels at the point of ligation permanently 
obliterated. 



506 



A TEXT-BOOK OF PATHOLOGY 



It has been asserted that generalized thrombo-angiitis is an infective 
process or has infiltrative, if not, indeed, suppurative, lesions as its char- 
acteristic early manifestation. It is most often seen in the extremities 
associated with subcutaneous nodosities. 

The changes affect mainly the intima and the adventitia, both 
of which coats are densely infiltrated with round cells. The thrombus, 
which was the original cause of the arteritis or which has resulted 
therefrom, becomes similarly infiltrated with round cells, and as the 
process advances is found to be penetrated by fibroblastic cells, which 
probably take origin from proliferation of the endothelial lining cells or 
from other connective-tissue cells in the walls of the vessels. New blood- 




Fig. 211. — Septic thrombo-endo-arteritis of coronary in vegetative endocarditis. 

vessels spring from the vasa vasdrwn and penetrate the thrombus, and a 
lesser number of new vessels may enter the thrombus directly from the 
lumen of the occluded vessel itself (see Fig. 8). The process of organiza- 
tion takes place as in the serous surfaces generally, and as new connec- 
tive tissue is formed the thrombus is gradually removed and the lumen 
of the vessel may become completely obliterated (endarteritis obliterans). 
Less extensive involvement of the vessel may lead to the formation of 
bands of adhesion passing from one side of the vessel to the other, and 
causing considerable deformity and distortion. In other cases there 
may be merely thickening of the intima as a final result, the thrombus 
having been washed away or absorbed. The media usually takes very 
little part in the process, being merely infiltrated with round cells, but the 



DISEASES OF THE CIRCULATORY SYSTEM 507 



entire wall of the vessel may become fibroid in the terminal stages and 
the separate coats may be indistinguishable. 

Peri-arteritis Nodosa. — Under this name has been described a form 
of productive inflammation of the adventitia leading to the formation 
of fibrous nodules. In some of these cases there is no doubt a different 
pathology, as in the instances in which the intima has been found to 
protrude in a hernia-like manner through defects in the media, but in 
most cases the disease is a productive peri-arteritis (see also under 
Aneurysm). The medial changes seem secondary, this coat showing 
necroses and hemorrhages, and finally atrophy. Intimal thickening 
occurs later. The disease is an acute one frequently and has been as- 
scribed to syphilis. The etiology cannot always be established. 

Arteriosclerosis 

Arteriosclerosis, or endarteritis chronica deformans, is a chronic 
degenerative and inflammatory disease of the arterial system. It may 
be confined to the arteries, or may be more extensive, involving the 
capillaries as well, when the term arteriocapiUary fibrosis (Gull and 
Sutton) is applicable. Sometimes the veins also are involved, and for 
this condition the name angiosclerosis has been proposed. 

Etiology. — Arteriosclerosis is a physiological process of old age, and 
probably begins as early as middle life in most persons. The earlier 
occurrence of the disease or the more extreme grades of its severity are 
dependent upon a variety of causes, among which certain chronic intoxi- 
cations — viz., syphilis, gout, chronic alcoholism, and chronic nephritis — 
are prominent. An important cause is muscular exertion, and it is not 
uncommon to find marked instances in persons whose life or occupation 
has subjected them to unusual muscular strain. Cachectic conditions 
of various kinds may play a part, as in cases of carcinoma, tuberculosis, 
or inanition; and sometimes the chronic arterial disease follows after 
acute infections, such as rheumatism, scarlet fever, typhoid fever, and 
the like. Overfeeding may be an important cause. 

Pathogenesis. — Not a little difference of opinion has existed in 
regard to the manner in which the recognized causes of arteriosclerosis 
operate. At first it was generally maintained that the infectious and 
toxic agencies directly irritate the inner lining of the blood-vessels and 
produce inflammatory thickening. This view has, however, been quite 
generally abandoned, and it now seems established that degenerative 
changes and loss of elasticity in the vessel wall are the result of the prim- 
itive causes, and that the hyperplastic processes in the intima and other 
parts of the arterial wall are the ultimate expression of a reparative 
process. 

In cases of arteriosclerosis occurring in old age, for example, the 
first disturbance of the blood-vessel consists in a loss of elasticity in 
the muscularis and an overdilatation of the blood-vessels. Secondarily, 
in consequence of this loss of elasticity, there is a hyperplasia of the 
intima, which serves in some measure to contract the lumen of the 



508 



A TEXT-BOOK OF PATHOLOGY 



vessels and thus restore the vascular channels to their normal calibre. 
In cases of purely pathological arteriosclerosis similar functional weak- 
ness of the muscularis or more pronounced and demonstrable degenera- 
tive changes may be the primary conditions, which in the end lead to 
arteriosclerosis. In all cases the direct effect of elevations of blood-pres- 
sure may play an important part, and in cases of muscular overwork or 
of hypertrophy of the heart the increased vascular tension may be the 
all-important cause. It may be said that generally sclerotic changes 
occur most frequently in vessels that feel, or are subject to, frequent 
alterations in blood-pressure. 

In explaining the minuter origin of the vessel-wall changes one must 
think of those which begin as a chronic productive inflammatory process 
and those in which the change is degenerative at first. The line between 
is by no means sharp, and the latter may be but a forerunner of the 
former. The inflammatory kind is exemplified by syphilitic arteritis 
(q. v.) ; the degenerative, by the senile form. 

It has been supposed by some that degenerations of the media, 
with giving away of its muscular, elastic, and fibrous tissue, are due 
to compression by proliferated intimal endothelium acting under toxic 
influences. These alterations have been explained by others as purely 
toxic degenerative medial changes. Regardless of inception, the pro- 
liferation of the intima and the degenerated media are replaced by 
connective tissue or by atheroma. In the senile form, granular, fatty, 
and calcareous degeneration of the media is the first change. Aschoff 
has suggested that in some way plasma penetrates the vessel walls, 
liberating colloids and inorganic salts which would act as a starting- 
point of degenerative or proliferative processes. 

In the Monckeberg type of sclerosis, affecting either large or small 
vessels, the medial coat is most prominently affected. Degeneration 
and calcification appear early, the muscle-fibers shortly disappear, and 
with the loss of tissue, which acts to regulate the caliber of the vessel, 
irregular dilatation of the lumen results. 

Pathological Anatomy. — Arteriosclerosis may be a diffuse process, 
affecting more or less uniformly a large part of the arterial system, or 
it may be a circumscribed or nodular condition. In the latter instances, 
which are most common in the aorta and large vessels, there are seen 
on the inner lining of the vessel nodular elevations, varying from the 
merest points to areas the size of a small coin. These are raised a milli- 
meter or two above the surface, and in their earlier stages have a trans- 
lucent grayish color; they are covered with smooth, unaltered endo- 
thelium. Later, degenerative changes ensue and the nodule becomes 
dull-white or yellowish in color, and finally calcification may render it 
extremely hard (atheromatous plate). The focus may, on the other hand, 
soften completely by degeneration and may discharge into the lumen of 
the vessel, leaving a necrotic, ulcerated patch (atheromatous idcer). 
Calcareous change may now occur, and the surface may be covered 
with thrombotic fibrinous deposits. These circumscribed areas of 
arteriosclerosis may be few in number and widely separated. In such 



DISEASES OF THE CIRCULATORY SYSTEM 



509 



cases the openings into the coronary arteries and the other branches 
of the aorta are the favorite seats. In other cases the plates may be 
so numerous and thickly set that the aorta is completely transformed. 

Diffuse arteriosclerosis is. es- 
pecially frequent in elderly per- 
sons, and is more common in the 
small vessels than in the aorta. 
Sometimes it is associated with 
the nodular form; sometimes the 
nodular change is wanting. 

Microscopically, the nodular 
elevations are found to consist of 
dense sclerotic tissue in which 
deeply staining cells of elongated 
character may be visible, the 
hyperplasia affecting the subendo- 
thelial part of the intima in the 
earliest stages (Fig. 212). There 
is swelling of the endothelia, 
with fatty detritus and globules 
collecting in these cells, pos- 
sibly the collection of fibrin upon the surface, and the appearance of 
polynuclears. Subsequently degeneration of the nodule becomes mani- 
fest. At first the intercellular material assumes a hyaline character and 
becomes glassy in appearance. The cells themselves may suffer fatty 




Fig. 213. — Atheromatous degeneration of a cerebral artery (Karg and Schmorl). 

degeneration from pressure. Later the whole area undergoes myxoma- 
tous or, more particularly, fatty degeneration, and breaks down, forming 
a pultaceous detritus in which fat-drops and cholesterol plates are 
prominent (Fig. 213). Eventually calcareous granules are deposited. 
In diffuse arteriosclerosis the changes resemble those met with in the 
nodular form. There is widespread thickening of the arterial coats in- 




Fig. 212. — Transverse section of a cere- 
bral vessel, in a case of endarteritis nodosa 
(Birch-Hirschfeld). 



510 



A TEXT-BOOK OF PATHOLOGY 



volving the subendothelial tissue at first and later the entire wall. 
Secondary degenerative changes in areas or patches occur in the large 
arteries, but are less common in the small vessels. The endothelium 
attempts repair over defects except calcareous ulcers. It is heaped up 
over subintimal and medial swellings. 

Fatty degeneration and calcification may also be apparent in the 
media, and more or less hyperplastic connective-tissue overgrowth 
may be seen in the adventitia. In cases of diffuse arteriosclerosis the 
media, as a rule, is thickened by hypertrophy of the muscle-fibers as 
well as by sclerosis; but in the nodular forms the media is usually dis- 
tinctly thinner than normal. This hypertrophy only affects those that 
are wholly intact and is compensatory, as destroyed media muscle- 
fibers do not regenerate. Repair occurs in direct relation to the freedom 
of blood-supply to the diseased parts, either from the vasa vasorum or 
from the lumen of the affected vessel. This brings nutrition and stimu- 
lates cells of the fibroblastic series. Even elastic fibers may be restored. 
Koster pointed out that round-cell infiltration surrounding the small 
branches of the vasa vasorum in the media is the earliest change in some 
instances. Rupture of the elastic coat is doubtless an important early 
change in many cases. Considerable round-cell infiltration may be seen 
in the deeper layers of the intima and in the media, and new formation 
of blood-vessels may be quite pronounced. Such changes, however, 
are not usual and not characteristic. 

Results. — In the smaller blood-vessels, particularly in those of 
the brain, the hyperplastic process in the intima may proceed to such 
a degree that the lumen of the vessels is almost completely obliter- 
ated (endarteritis obliterans). Complete obliteration may take place 
by direct union of the opposite walls of the vessel, or there may be first 
thrombosis, with subsequent organization of the thrombus. In the 
aorta and in some of its larger branches the loss of elasticity consequent 
upon the formation of fibrous tissue and subsequent degenerations leads 
to gradual dilatation of the blood-vessel walls, either in the form of dif- 
fuse ectasia or of localized aneurysmal sacs. Sometimes the degenera- 
tion of the diseased area occasions spontaneous rupture of the vessel. 

Portions of the thrombotic deposits upon the roughened lining 
of the vessels, or portions of the degenerative tissue itself, may be 
discharged into the circulation, and may be carried to the peripheral 
parts as emboli. 

Changes in Other Organs. — Diffuse arteriosclerosis places an im- 
pediment upon the heart which leads to hypertrophy of its walls, and, in 
particular, of the walls of the left ventricle. 

When the process affects the small blood-vessels in the substance 
of the various organs, degenerative changes due to anemia and react- 
ive hyperplasia of connective tissue are common results. Thus, in 
cases of sclerosis affecting the cerebral vessels, cerebral softening is 
commonly met with, while in cases in which the branches of the coronary 
or of the renal arteries are affected, degeneration and fibroid changes are 
seen in the heart and kidneys. 



DISEASES OF THE CIRCULATORY SYSTEM 



511 



INFECTIOUS DISEASES 

Syphilis may involve the blood-vessels in a variety of ways. No 
doubt syphilitic infection is a most potent cause in the production of 
arteriosclerosis, but more specific involvement of the vessels occurs. 
Recent investigators have described a special type of arteriosclerosis 
as syphilitic. In this the ascending aorta is often notably affected, 
the lesions presenting themselves as scar-like changes which cause 
marked deformity of the endarterial surface. This can proceed toward 
the heart and affect the valve bases or the leaflets themselves. Micro- 
scopically, the media and adventitia are much more decidedly in- 
volved than in ordinary arteriosclerosis. The process begins as a peri- 
vasa-vasorum infiltrate of round cells in the media and adventitia, 
shortly followed by atrophy of muscularis and elastica. In areas of 
syphilitic infiltration and induration or adjoining gummata the small 
blood-vessels present noteworthy changes. The intima and the ad- 
ventitia, but particularly the former, undergo great hyperplasia, and the 
lumen of the vessel may be almost obliterated. The changes are first 
noted in the intima, where large numbers of epithelioid cells are formed, 
while, later, infiltration of round cells is observed. The adventitia is 
similarly, but less extensively, affected. The outcome of this arteritis 
is fibrous scar-tissue; atheroma and calcification occur very seldom 
in pure syphilitic arteritis. The scar-tissue, while dense, is without 
elasticity, so that at the points of cicatrization variations of lumen occur 
(syphilitic aneurysms, q. v.). 

Tuberculosis. — The arteries may become involved in areas of tuber- 
culosis, though, as a rule, they prove resistant for a long time. Typical 
caseous degeneration may be seen in the walls of the blood-vessels, 
beginning in the adventitia and gradually advancing toward the inte- 
rior. In the lungs these changes are not infrequently seen in the walls 
of tuberculous cavities, and as a result there may be small aneurysmal 
dilatations at the points where the wall of the vessel has become eroded 
and weakened. It is from such vessels that the severe hemorrhages of 
the late stages of phthisis take place. Sometimes the blood-vessels 
of the tuberculous area present productive change leading to great 
thickening of the adventitia and of the intima, and there may be con- 
siderable narrowing of the lumen of the vessel. This, however, is less 
common than the degenerative changes before alluded to. There may 
be solitary tubercles in the intima or subintimal layers of the media. 
They are of ordinary architecture and may open into the vessel lumen. 
They start as endothelial tubercles when the organisms are taken up 
by these lining cells in capillaries. 

ANEURYSM 

Definition. — By aneurysm is meant a more or less localized dilata- 
tion of the arterial walls. The term has, however, been applied also to 
collections of blood outside of an artery enclosed by an adventitious 



512 



A TEXT-BOOK OF PATHOLOGY 



wall and consequent upon a rupture of the vessel. The name false or 
spurious aneurysm has been specially applied to such cases, while the 
term true aneurysm is reserved for such as conform to the first defini- 
tion. It is preferable to confine the single word aneurysm to the 
latter. 

Etiology. — Aneurysms are always due to some weakness of the 
walls of the. blood-vessel and to the distending force of the blood within. 
It is, therefore, most common to find the disease in persons beyond the 
age of forty or forty-five years, and particularly in those who have 
acquired arteriosclerosis. Among the remote causes, therefore, are 
those of arterial disease — syphilitis, gout, alcoholism, lead-poisoning, 
and other chronic intoxications. Of all the causes, syphilis is most impor- 
tant. Sometimes it would seem that there is hereditary weakness of the 

arterial coats, and instances of aneu- 
rysm occurring in successive genera- 
tions have been recorded. Even con- 
genital aneurysms have been observed. 
As contributing causes may be ranked 
all conditions which increase the blood- 
pressure. Thus, laborious occupations, 
hypertrophy of the heart, and dis- 
eases which occasion constant excess 
of blood-pressure give rise to arterial 
degeneration and also to dilatation 
of the vessel in a purely mechanical 
way. Sudden aneurysmal dilatation 
of a weakened vessel may occur 
after severe straining efforts, as in 
coughing, during labor, in the strain- 
ing of obstinate constipation, etc. 

More acute degenerative changes 
in the blood-vessels may lead to 
aneurysmal dilatations. Thus, in the 
rare instances of acute aortitis in 
Fig. 214. — Worm aneurysm of the association with malignant endocar- 
horse (Leuckart). ditis, small aneurysmal dilatations 

and even rupture of the aorta may occur. Embolism plays a part 
in a similar manner. Sometimes a calcareous embolus from a diseased 
valve of the heart, or from an atheromatous plate in the aorta, may 
lacerate the walls of a peripheral vessel, leading to the formation of a 
dilatation. In other cases infected emboli (as in malignant endocarditis 
or thrombosis with secondary degeneration of the clot) lodge in the 
peripheral vessels and occasion acute inflammatory or degenerative 
lesions of the walls, and eventually aneurysmal dilatation. These 
cases are analogous to the aneurysms of lower animals caused by 
animal parasites (Fig. 214). 

The artery most commonly affected is the aorta, and in particular 
the thoracic portion. A majority of the aneurysms affecting the thoracic 




DISEASES OF THE CIRCULATORY SYSTEM 



513 



part of this vessel arise from the ascending limb, and not rarely it is one 
of the sinuses of Valsalva that first suffers dilatation. Next to the 
aorta in point of frequency, the popliteal, femoral, carotid, subclavian, 
innominate, axillary, and iliac vessels are affected. 

An interesting form, and one of great frequency and clinical sig- 
nificance, is that which affects the small blood-vessels of the brain, par- 
ticularly the branches supplying the lenticulostriate body. This is the 
so-called miliary aneurysm, which is commonly the cause of cerebral 
hemorrhage (Fig. 215). It is simply a small saccular aneurysm due to 
weakening of the blood-vessel walls by 
sclerosis or degeneration. 

In some cases of the condition de- 
scribed as peri-arteritis nodosa (see p. 
507) there has been discovered a hernia- 
like projection of the intima through 
defects of the media. These have been 
recorded as instances of congenital 
aneurysm, but this explanation does not 
suffice for all cases. (See Arteritis.) 

In phthisical lungs there are often 
found somewhat similar hernia-like 
aneurysms, due to erosion of the ad- 
ventitia and media by the tuberculous process; and it is from these 
that the severe hemorrhages of the late stages of phthisis occur. 

Pathological Anatomy. — Aneurysms may be of three kinds: (1) 
Those in which there is quite general dilatation of all of the coats of the 
vessel, which, therefore, present themselves in the form of a more or less 
uniform dilatation (ectatic aneurysm) ; (2) those in which a local weaken- 
ing leads to the formation of a saccular pouch, often communicating with 
the artery by a narrowed orifice (saccular aneurysm); and (3) those in 
which a rupture of the intima, and usually of portions of the media as 
well, has led to infiltration of blood between the tunics of the vessel 
wall (dissecting aneurysm). 

1. Ectatic Aneurysm. — There is more or less uniform dilatation in 
these cases, and there may be distinguished fusiform or spi?idle-shaped 
and cylindrical varieties, according to the shape assumed (Fig. 216) 
In some instances the vessel is rendered tortuous by the unequal involve- 
ment of different portions, and to this form the term cirsoid aneurysm 
may be applied. The same term, as well as the name anastomotic 
aneurysm, is given to certain conditions of the arteries of the scalp and 
other parts which lead to the formation of tortuous vessels standing out 
prominently beneath the skin; but these are instances rather of hyper- 
trophy of the coats, with increase of length and thickness of the walls, 
without, in reality, any aneurysmal dilatation at all. 

In ectatic aneurysms the intima and adventitia are usually thickened, 
and there are generally atheromatous patches in the former. The media 
is generally thinner than normal, and may be actually deficient in places. 
Ectatic aneurysms may show a certain amount of thrombosis in the form 

33 




Fig. 215. — Miliary aneurysm of the 



514 



A TEXT-BOOK OF PATHOLOGY 



of laminated clots, when there are pouehings or inequalities in the dila- 
tation, but very frequently there is no thrombosis. 

2. Saccular Aneurysm. — This is the most important variety. Ac- 
cording to Thoma and others, the first step in the process is the weak- 
ening or giving way of the media, followed by gradual dilatation of the 
intima and adventitia. There results a saccular dilatation commu- 
nicating with an artery, from which it arises by a more or less narrow 
orifice (Figs. 217-219). The aneurysmal sac grows larger and larger, and 

may eventually rupture; but even 




inal aorta : an opening has been made to _._,„„ , 

show the clot within (from a specimen , Fl §- 217.— Saccular aneurysm of the arch of 

in the Museum of the Philadelphia the aorta . projecting forward and attached to 

Hospital). the rlbs (Ziegler). 



and intima, the media being usually thinned and often completely 
wanting. The intima is generally covered with atheromatous plates, 
and the cavity, as a rule, contains more or less abundant laminated clots, 
which tend to contract and organize, or to suffer subsequent degenera- 
tion. The aneurysm, if small, may be completely healed by the organiza- 
tion of the clots within. 

The tissues surrounding the aneurysm are pushed aside or com- 
pressed, and may suffer extensive necrosis. In cases of aneurysm of the 
thoracic aorta the sternum and ribs may be eroded, and the aneurysm 



DISEASES OF THE CIRCULATORY SYSTEM 



515 



may project beneath the skin anteriorly and eventually rupture (Fig. 

220) . In other cases the trachea, bronchial tubes, or lungs are com- 
pressed, and rupture takes place through the trachea or bronchi (Fig. 

221) . In still others the sac projects posteriorly, erodes the bodies of 
the vertebra? and ribs, and may compress the spinal cord or may project 
beneath the tissues of the back. Occasionally, communication is 
established with the large venous trunks, particularly the descending 
vena cava. Complete arrest or cure of an aneurysm may take place by 
organization of the clots contained, but such a result is rare. 




Fig. 218. — Saccular and partly ectatic aneu- Fig. 219. — Saccular aneurysm of 

rysm of the descending part of the arch of the aorta the ascending part of the arch of the 

(from a specimen in the Museum of the Philadel- aorta (from a specimen in the Mu- 

phia Hospital). seum of the Philadelphia Hospital). 



3. Dissecting aneurysm is most common in the aorta. As the 
result of degenerative lesions or of mechanical injury rupture of the 
intima occurs, and the blood finds its way between the coats of the 
artery, often burrowing to considerable distances. In a case under 
the observation of one of the authors the walls of the aorta were dis- 
sected as far as the bifurcation, where secondary ruptures had occurred 
in the intima (Fig. 222). Usually the dissection takes place in the 
media, which is thus separated into two parts. Subsequently the ad- 
ventitious canal may become lined with endothelium, arid in the case 
quoted atheromatous plates had formed in the latter. 



516 



A TEXT-BOOK OF PATHOLOGY 



Associated Conditions in Other Parts. — Some hypertrophy of the 
heart may occur when an aneurysm is situated near the root of the 
aorta, and particularly in instances in which direct pressure is brought 




Fig. 220. — Aneurysm of the aorta: erosion of the sternum and projection of the sac 

beneath the skin. 

to bear upon the heart. As a rule, however, the amount of hyper- 
trophy is much less than might be expected. Pressure upon the venous 




Fig. 221. — The trachea, showing perforation of an aneurysm of the aorta (from a specimen 
in the Museum of the Philadelphia Hospital). 

channels is an early manifestation, and leads to passive congestion and 
often to dropsy and cyanosis. Necrosis of the parts which are directly 
compressed has already been alluded to. Portions of the clot within 



DISEASES OF THE CIRCULATORY SYSTEM 



517 



the aneurysmal cavity not rarely become separated, and are carried as 
emboli to the peripheral parts of the circulation. 

False or spurious aneurysms most commonly result from trauma- 
tism, though sometimes spontaneous rupture of the vessel is the imme- 
diate cause. The blood may find its way from the ruptured artery into 
the surrounding tissues, forming a blood-tumor, or hematoma, which 
becomes encapsulated by condensation of the surrounding tissues and 
by reactive overgrowth of connective tissue stimulated to activity by the 
fibrin formation and liberation of leukocytes. The retaining wall thus 
formed may in some cases be lined with endothelial cells, and secondary 
inflammatory thickening or atheromatous plates may form. When an 
artery and vein are both injured, as is sometimes the case in phlebotomy, 
the blood may enter the vein and distend this markedly. The term 
aneurysmal varix is applied to such cases. In other instances the artery 



Fig. 222. — Dissecting aneurysm of the aorta: the aneurysm began near the aortic 
valves and extended to the iliac branches, converting the aorta into a double tube: 
a, Transverse section; b, longitudinal section. 

and vein communicate by an intermediate sac formed by the condensa- 
tion of the intervening tissues, and for such the name varicose aneurysm 
is used. Aneurysms may arise when by erosion of the adventitia and 
outer media the support of the vessel is so weakened that dilatation 
occurs in the direction of this lessened resistance. 



Anatomical Considerations. — The veins resemble the arteries, 
excepting that the muscular coat is less well developed, and that most 
of the veins are supplied with endothelial reduplications or folds, which 
act as valves and prevent the backward flow of the blood. 



Thrombosis of the veins is the most important condition. This, 
however,, has been sufficiently considered under Thrombosis (see p. 67). 




The Veins 



CIRCULATORY DISTURBANCES 



518 



A TEXT-BOOK OF PATHOLOGY 



DEGENERATIONS 

Fatty degeneration of the intima and media may occur as in the 
arteries, but it is comparatively rare and unimportant. 

Calcification is met with in veins which have become dilated or 
varicose, or otherwise diseased. 

INFLAMMATION, OR PHLEBITIS 

Acute phlebitis is a comparatively common affection. It may 
occur as the result of inflammation, particularly of infectious nature, 
in the neighborhood of the vein. In such cases the outer coat is first 
involved, and the term "periphlebitis" is properly applied. This 
condition is met with in association with infected wounds and phleg- 
monous inflammations of the subcutaneous tissues. The veins beneath 
the skin may be distinctly visible as blue streaks running in various 
directions. Microscopically, there is found to be an invasion of the 
adventitia with round cells, and actual foci of suppuration are not un- 
common. The cellular infiltration may extend to the media and some- 




Fig. 223. — Thrombophlebitis of the femoral vein (from a specimen in the Museum of the 

Philadelphia Hospital). 

times to the intima, and not rarely thrombosis occurs within. The 
thrombi thus formed may secondarily become infected, soften, and 
occasion septic embolism. 

In another group of cases phlebitis begins from within, and is the 
consequence of primary thrombosis of the vein (Figs. 223 and 224). 
To such the name thrombophlebitis is applicable. The histological 
changes are similar in these to those which occur in thrombo-arteritis, 
and as terminal results localized thickening of the venous wall or irreg- 
ular contractions by the formation of fibrous adhesions and even com- 
plete obliteration of the venous channel may result. When the thrombus 
is thus organized or partially organized calcification may eventually 
occur, and in this manner phleboliths, or vein-stones, are formed. 

Chronic phlebitis, or phlebosclerosis, corresponds to chronic arte- 
ritis or arteriosclerosis. A certain amount of chronic inflammatory thick- 
ening of the vein ensues as a consequence of thrombophlebitis. _ Phlebo- 
sclerosis may also be due to overdistention of a vein resulting from 
thrombosis or other forms of obstruction, and thus plays a secondary 
part in dilatation of the veins, or phlebectasia. 

Phlebosclerosis may, however, occur as a widespread affection in 



DISEASES OF THE CIRCULATORY SYSTEM 



519 



association with arteriosclerosis, though rarely in equal degree, in con- 
sequence of certain systemic conditions — syphilis, alcohol, gout, etc. 
The changes occurring in the vein are much the same as those in the 
artery, but the new-formed fibrous tissue in the intima less commonly 
undergoes degenerative changes and calcification than in arterial scle- 
rosis. Sections of the affected veins show, as a rule, absence of signs 
of inflammation and of marked degeneration. The essential change is a 
proliferation of the cells of the intima and of the connective tissue of 
the media. The condition resembles more a functional hyperplasia, the 
result of mechanical forces, than a chronic inflammation. 




<■':. > 



Fig. 224. — Phlebitis and periphlebitis of the umbilical vein of the newborn: purulent 
infiltration of the intima and adventitia: calcareous particles in the media (Birch-Hirsch- 
feld). 

In cases of congenital syphilis an interesting form of thickening of 
the intima, leading to stenosis or even complete obstruction, has been 
found in the veins of the umbilical cord, and less frequently in the 
portal vein. Similar hyperplastic endophlebitis has been found in the 
veins of the extremities in syphilis of adults. 

DILATATION OF THE VEINS; PHLEBECTASIA; VARICOSITY 

Etiology. — Dilatation of the veins occurs from mechanical obstruc- 
tion to the circulation or from weakness of their walls. It presents itself 
more commonly in dependent portions of the body, and is particularly 
frequent in the veins of the legs, of the rectum, of the neck of the bladder, 
of the spermatic cord, of the scrotum, and of the vagina. 



520 



A TEXT-BOOK OF PATHOLOGY 



Mechanical causes are most important. Thus, in cases of cirrhosis 
of the liver, of obstinate constipation, and of pelvic tumors, dilatation of 
the veins of the rectum, causing hemorrhoids, is frequent. In cases of 
abdominal tumors, repeated pregnancy, or other causes of obstruction 
to the venous return of the blood from the lower extremities, varicosity 
of the veins of the legs is frequently observed. Always, however, local 
disease of the veins themselves tends to make the dilatations more 
pronounced, and, in addition, systemic depression and, particularly, car- 
diac weakness are contributing causes which operate by aiding in the 
stagnation of the blood, which otherwise might pass by collateral 
channels to its proper destination. 

Pathological Anatomy. — The veins in phlebectasia become dilated 
and also elongated, so that they soon assume a tortuous character. Not 
rarely masses of much-dilated veins lie closely aggregated in groups or 
clumps beneath the surface of the skin; and communications may be 
established between the adjoining pouches of dilatation, and thus a 
cavernous tissue is formed. The walls of the dilated veins are usually 
considerably thickened (phlebosclerosis), and even calcification may 
occur in the intima. 

Results. — The circulation of the blood is slowed and thrombosis is, 
therefore, frequent. The thrombi may undergo organization or calci- 
fication, or in other cases may soften and occasion embolism. When 
varicosities are established in the veins of any submucous tissue, catar- 
rhal inflammation of the overlying mucosa is occasioned and generally 
proves obstinate. At the same time a certain amount of hyperplasia of 
the connective tissue between the dilated veins takes place and thicken- 
ing of the mucous membrane results. When the subcutaneous veins are 
involved the skin is prone to become thickened and to present eczema- 
tous inflammation, while the subcutaneous tissue may be greatly in- 
creased in thickness and density (phlebectatic elephantiasis or pachy- 
dermia). Not rarely ulcerations of the skin of the lower extremity owe 
their origin to varicosity of the veins, and such ulcers are prone to prove 
indolent and obstinate. Hemorrhage may occur from varicosities of the 
submucous veins, particularly in case of hemorrhoids and in the esopha- 
geal varicosities of drunkards. 

TUMORS 

Tumors rarely begin in the walls of the veins, though myoma and 
sarcoma have been described. More commonly the walls of the veins 
are secondarily involved in cases of tumors surrounding them. Aschoff 
lays stress upon the involvement of veins by leukemic infiltrates and 
myeloma. 

INFECTIOUS DISEASES 

Tuberculosis not rarely attacks the veins, particularly those of the 
lungs. Perforation of the wall may take place, and miliary tubercu- 
losis is a frequent consequence. 

Syphilis of the veins has already been referred to. 



DISEASES OF THE CIRCULATORY SYSTEM 



521 



THE LYMPHATIC CHANNELS 

Anatomical Considerations. — The lymphatic system begins in the 
lymph-spaces, which are the spaces between the tissue elements in all 
parts of the body. These lymph-spaces unite to form definite lymphatic 
capillaries, which are channels having walls composed of a single layer 
of endothelial cells. The lymphatic capillaries unite to form larger 
vessels, and in these connective-tissue coats support the endothelial 
lining. 

Lymph coagulates very slowly — ten to twenty minutes — due to 
the small amount of thrombokinase in it. Intralymphatic thrombosis 
does occur after ligation, but it is much favored by destruction of tissue 
locally, such a condition freeing thrombokinase. Opie has shown this 
by addition of tissue extracts to freshly drawn lymph. Bacterial inva- 
sion of lymph-channels assists in freeing thrombokinase. 

INFLAMMATION 

Inflammation of the lymphatic vessels, or lymphangitis, is 

always secondary to inflammatory affections of the parts surrounding the 
lymphatics, or of those parts from which the lymphatics take their 
origin. In cases of infective lesions of the extremities, red lines, indi- 
cating the position and course of the inflamed lymphatics, may not in- 
frequently be seen beneath she skin, extending upward to the nearest 
lymphatic glands. Histologically, the first change in such cases is 
swelling and ofttimes multiplication of the endothelial cells of the 
lymphatic vessel; later, there may be accumulation of leukocytes within, 
and the lymphatic channel may be uniformly filled with pus or dis- 
tended at different points. Usually a certain amount of perilymphangi- 
tis accompanies the process, and in cases of violent septic infection the 
surrounding tissues may become extensively involved in phlegmonous 
inflammation. Thrombosis may take place within the lymphatic channel 
in cases of moderate severity and thus obstruction ensue. The termina- 
tion is either in resolution or suppuration, with more or less widespread 
involvement of the surrounding tissues. Resolution may be only 
partial, the inflammatory changes going on to the formation of con- 
nective tissue, which may obliterate the channels, or the restitution of 
the wall of the lymphatic vessel may be imperfect and subsequent 
dilatation results. 

A primary chronic lymphangitis may arise from prolonged obstruc- 
tion to the lymph flow or by continued irritation, as by foreign particles 
which the channels are draining to the lymph-nodes. The vessels are 
changed to a solid band of endothelial cells surrounded by a thickened 
fibrous coat. 

DILATATION OF THE LYMPHATICS, OR LYMPHANGIECTASIA 

This condition may be an acquired or a congenital affection. 
Acquired dilatation of the lymphatics results from obstruction to 
the larger channels, as in cases of pressure upon or thrombosis of the 



522 



A TEXT-BOOK OF PATHOLOGY 



thoracic duct, or of obstruction of the lymphatic channels by filarial 
In other cases it is due to inflammations surrounding the lymphatics 
and leading to weakness of their walls. It is very commonly observed 
in the subcutaneous lymphatics, and constitutes the endemic elephan- 
tiasis of warmer countries. This condition is particularly common in 
the lower extremities, scrotum, and labia, but may affect other parts. 
The skin is greatly thickened and the surface often of irregularly lobu- 
lated character. On incision into it there is found an abundant exuda- 
tion from the subcutaneous tissue of serous or of milky liquid. 

Obstructive dilatation of the intra-abdominal lymphatics is not 
unusual. Rupture of dilated branches in the genito-urinary tract 
may lead to chyluria; similarly, chylous ascites or hydrothorax may 
arise by obstruction or rupture of the thoracic duct. 

Congenital lymphangiectasia may take the form of a diffuse condi- 
tion affecting the lymphatics more or less regularly in certain parts of 
the body, or it may appear in circumscribed areas, often in situations 
in which the ordinary lymphatic supply is not abundant. The diffuse 
form occasionally presents itself in the newborn in the form of edema- 
tous or semicystic swellings of the subcutaneous tissue, resembling those 
of elephantiasis. In the same group of cases belong the instances of con- 
genital enlargement of the tongue {macroglossia) and of the lips (macro- 
cheilia). In some of these instances the development of the condition 
does not occur until some time after birth, though the process is, in 
reality, congenital. Localized lymphatic dilatations constitute the form 
of new growth known as lymphangioma. (See General Pathology.) 

INFECTIOUS DISEASES 

Tuberculosis. — The lymphatics play an important part in the dis- 
semination of tuberculosis within the organs, and they may themselves 
be involved in the disease. This is beautifully illustrated in cases of 
intestinal tuberculosis with ulceration. In such cases the lymphatic 
channels in the serous coat may be seen radiating from a point opposite 
the ulceration toward the mesentery, and small miliary nodules are 
seen in their course. 

Syphilis. — The lymphatics may be involved in syphilitic processes 
in their vicinity, but the changes are not characteristic. 

TUMORS 

In addition to the lymphangiomata referred to, the lymphatic vessels 
are the primary seat of tumors resulting from multiplication of the 
lining endothelial cells, which are known as endotheliomata. These 
tumors are especially common in the serous surfaces, but may also be 
met with in the skin and elsewhere. The lymphatics bear an important 
relation to the metastasis of malignant tumors, particularly of carcino- 
mata. The carcinoma cells enter the lymphatics and are carried by 
the stream to distant parts of the body; sometimes the lymphatics near 
carcinomata are found densely packed with cancer cells. 



DISEASES OF THE CIRCULATORY SYSTEM 



523 



PARASITES 

The adult of the Filaria bancrofti resides in the lymphatic vessels, 
and the embryos may be present in large numbers. (See General 
Pathology.) 

The Thoracic Duct 

Pathological processes involving the thoracic duct resemble in 
general character those of the other lymphatic vessels, but the size of 
the duct and its anatomical relations make the diseases affecting it of 
somewhat greater significance than the same diseases when occurring 
in the smaller lymphatics. 

Thrombosis may occur in association with inflammation of the duct 
or without such, and there may be a permanent occlusion in consequence. 
Dilatation of the lower parts of the duct, as well as of the lymphatic 
vessels of the abdomen, may ensue, and sometimes the receptaculum 
or other portions of the duct may become cystic. Chylous ascites may 
likewise result. More commonly collateral circulation re-establishes 
communications and serious consequences are not observed. 

Dilatation of the thoracic duct may also result directly from cardiac 
failure with engorgement of the greater veins. The outflow of lymph 
is impeded, and in some cases the backward pressure of the blood 
through the superior cava may fill and distend the upper part of the 
thoracic duct with blood. 

Inflammation occurs in consequence of various inflammatory dis- 
eases of the abdomen or of the pelvis, by the invasion of irritants through 
the lymph received from the affected areas. There may also be direct 
extension of inflammation in cases of abdominal disease, or in pleurisy 
or other intrathoracic affections. 

Tuberculosis affecting the abdominal portion of the duct is some- 
times observed in cases of intestinal or mesenteric tuberculosis, and 
may occasion secondary miliary tuberculosis, particularly the form in 
which the disease is subacute or chronic in its course (Weigert). It 
occurs in periductal or intimal form. In the latter case it may be either 
as a soft spreading lesion leading to erosion and ulceration, or as a poly- 
poid outgrowth into the lumen. 

Tumors. — Primary tumors (sarcoma, fibroma) are sometimes ob- 
served, and secondary carcinoma is more commonly met with. 



CHAPTER IV 



DISEASES OF THE RESPIRATORY SYSTEM 

The Nasal Cavities 

Anatomical Considerations. — The mucous membrane of the nose 
is usually prominent, especially over the lower turbinated bone, where 
it is 4 mm. thick. In the lower or respiratory parts of the nose the 
epithelium is stratified, ciliated, columnar in type. The submucosa is 
replete with a venous network, giving it, particularly over the inferior 
turbinated bone, the appearance of erectile tissue. In the olfactory 
regions non-ciliated columnar cells, which become attenuated at the 
inner end, line the surface. Between the filiform prolongations within 
lie round and tapering olfactory cells. Small tubular and racemose serous 
and mucous glands are freely distributed in the mucosa. 

CONGENITAL ABNORMALITIES 

Deviations of the septum and other slight anomalies are common. 
Atresia, absence of the septum or other parts, or complete absence of 
the nose are rare defects. Harelip and cleft palate frequently involve 
the nasal cavities. 

CIRCULATORY DISTURBANCES 

Active hyperemia occurs in consequence of exposure to great heat 
or cold, or of ascending elevations, and when the heart is overstimulated. 
Certain odors or finely divided dust-particles may provoke transient 
congestion. Frequently, however, such congestion terminates in in- 
flammation. 

Passive hyperemia may be due to cardiac weakness, obstructive 
diseases of the lungs, and local pressure on veins. 

Hemorrhage. — In either passive or active congestion and in inflam- 
mations of the mucous membrane hemorrhage (epistaxis) may occur. 
Bleeding may also result from blood-diseases (hemophilia, pernicious 
anemia, leukemia), from disease of the blood-vessels (arteriosclerosis), 
or in a paroxysmal form from obscure causes. Epistaxis is a frequent 
prodromal symptom of typhoid fever; less frequently it occurs in 
influenza and other infections. Trauma may cause nosebleed. It also 
may occur vicariously when normal menstruation fails. 

Edema of the mucous membrane may be associated with inflam- 
mation. 

524 



DISEASES OF THE RESPIRATORY SYSTEM 



525 



INFLAMMATIONS 

Acute nasal catarrh (acute rhinitis, coryza) commonly results from 
exposure to cold. Irritant fumes may cause it; often it seems infectious 
and contagious. It may occur as an associated condition in various 
infections, as grip, typhoid fever, measles, etc. Hay-fever and its 
related disorders are forms of acute rhinitis. Gout and other nutri- 
tional disorders may predispose to rhinitis or cause it. The mucosa is at 
first intensely red and dry ; then an irritating serous, followed by mucous 
and finally mucopurulent, exudation is discharged. Herpes or ecze- 
matous eruptions of the lips are common. Considerable inflammatory 
edema of the mucous membrane of the nose and accessory cavities may 
occur. It may spread to the middle ear, to adjacent sinuses, or to the 
brain. This is especially true in the purulent form. Pyemia of the 
antrum of Highmore may start in this way. 

Chronic rhinitis follows repeated acute attacks, especially in 
tuberculous or syphilitic persons. The mucosa, especially over the 
inferior turbinated bone, becomes thickened (hypertrophic rhinitis) 
and may remain so, or undergo atrophy (rhinitis atrophica). In the 
atrophic form the exudate is scanty and appears as dry, greenish crusts, 
which sometimes occasion extensive ulcerations and become horribly 
offensive. To such cases the term ozena is applied. Various forms of 
bacilli and micrococci have been discovered, the most frequent being an 
organism resembling the bacillus of Friedlander, which is considered the 
cause of the disease by many observers. Fetid discharges may also 
occur in syphilitic or tuberculous diseases of the nose (ozama syphilitica 
sen tuberculosa). 

In the hypertrophic variety the openings of the sinuses about the 
nose may be slowly closed, with resultant chronic inflammation, which 
may lead to widespread phlegmon or necrosis. In this form there is 
increase of the submucosa and but little change in the epithelial layer, 
except for occasional glandular distention or distortion of mucous glands. 
While secondary atrophy may occur, what is called atrophic rhinitis 
(as above described) is said by some to be atrophic from the start, there 
being atrophy of both glands and supporting tissue. 

INFECTIOUS DISEASES 

Diphtheritic rhinitis is usually secondary to pharyngeal diphtheria. 
Primary diphtheritic rhinitis of rather benign character is occasionally 
observed. Non-specific pseudomembranous rhinitis is a very rare con- 
dition. 

Syphilis in the secondary stage and in congenital cases sometimes 
occasions simple catarrhal rhinitis. Mucous patches may occur, or 
gummata spring from the mucous membrane or from the periosteum 
or perichondrium. The latter tend to ulcerate and cause destruction. 
The purulent discharge may be fetid. 

Tuberculosis may occur as disseminated or aggregated tubercles 
of the mucous membrane, or as ulcers and carious processes. These 



526 



A TEXT-BOOK OF PATHOLOGY 



are all rare, but "scrofulous catarrhs" of children, probably often due to 
tuberculous lesions, are common. Lupus of the face may extend to the 
nose. 

Glanders occasions intense purulent and hemorrhagic rhinitis, or 
nodular growths with ulceration. Nodules and ulcers are common in 
leprosy. Irregular swelling and induration of the mucous membrane of 
the nose and the adjoining skin in rhinoscleroma are rare conditions. 

TUMORS 

The commonest form of tumor is the polyp, which is sometimes 
distinctly the result of hypertrophic rhinitis, at other times obscure in 
origin. Polypi present the ordinary structure of the nasal mucosa, 
with a tendency to cystic change from occlusion of the glands, or to 
adenomatous appearances from proliferation of the glandular elements. 
Fibroid, myxomatous, and sarcomatous polypi also occur. In all cases 
there is a tendency to recurrence after removal. A rare form of hairy 
polyp has been described. Chondromata, osteomata, sarcomata, and 
epithelial or glandular cancers may be found. 

PARASITES AND FOREIGN BODIES 

Larva? of various flies may occur in the nasal chambers and set up 
serious inflammatory lesions. Foreign bodies may become incrusted 
with lime-salts and lead to the formation of rhinoliths. These formations 
may also arise around a nucleus of epithelial crusts, mucus, or desqua- 
mated epithelia in obscure niches of the nasal cavity after prolonged 
catarrh. 

The sinuses (frontal, ethmoid, and sphenoid) and the antrum of 
Highmore are frequently involved in inflammations of the nasal mucosa, 
and when their outlets are obstructed by swelling of the nasal mucosa 
chronic lesions (catarrhal or suppurative) may occur. These may occa- 
sion generalized infections or infectious toxemias of various forms. 
Empyemata of the sinuses may open into the nose, the cranial cavity, 
the mouth, or may discharge externally. 

The Larynx 

Anatomical Considerations. — The lining epithelium of the larynx 
is stratified squamous as far as the false vocal cords. Below these and 
throughout the ventricles it is stratified, ciliated, columnar, and thus 
continues into the trachea and bronchi, excepting over the true vocal 
cords, which are covered with stratified squamous epithelium. The 
tunica propria contains much yellow elastic fiber, and the submucosa is 
quite loose, especially over the base of the epiglottis and the aryepi- 
glottic folds. 

CONGENITAL ABNORMALITIES 

Minor defects in shape of the constituent parts of the larynx are not 
rare. Congenital fistulse communicating with the exterior, and dilata- 



DISEASES OF THE RESPIRATORY SYSTEM 



527 



tion of the ventricles similar to the normal pouching found in certain 
monkeys, are occasionally met with. Abnormal largeness and smallness, 
the latter especially in persons having poorly developed sexual organs 
and those castrated early in life, are more frequent conditions. 

CIRCULATORY DISTURBANCES 

Anemia may occur in general anemia, and is sometimes found in 
tuberculous and chlorotic subjects in pronounced degrees. 

Active hyperemia follows exposure, overuse of the voice, and irri- 
tation by gases, dust, and the like. 

Passive hyperemia occurs in heart diseases, intrathoracic tumor, and 
other conditions obstructing the venous circulation. In active conges- 
tion the larynx is bright red; in passive congestion it is dark red in color, 
and distended veins may be prominent. • 

Hemorrhages are seen in the mucosa after death from asphyxia, 
in cases of purpura or other hemorrhagic conditions, as well as in intense 
inflammation of the larynx. Large hemorrhages may occur in cases of 
cancer. 

Edema of the epiglottis, the aryepiglottic folds, and other parts of 
the larynx may be part of anasarca in Bright's disease or heart dis- 
ease, or may result from local pressure upon the veins. The parts be- 
come greatly swollen and of an anemic, translucent appearance. Great 
stenosis of the larynx commonly results. Generally "edema of the 
larynx" is inflammatory in nature (see below). 

INFLAMMATIONS 

Acute catarrhal laryngitis results from chemical or mechanical 
irritation; it accompanies whooping-cough, measles, small-pox, typhoid 
fever, and other infections. The mucous membrane is bright red and 
swollen. A scanty mucous or mucopurulent exudate is usually noted. 
Intense laryngitis is attended with small hemorrhagic ecchymoses or 
erosions; true ulcers are rare. Follicular ulcers are sometimes seen, and 
rarely small vesicles arise upon the surface (herpetic laryngitis). 

As is the case with all surface inflammations, laryngitis may assume 
a catarrhal, fibrinous, pseudomembranous, purulent, or ulcerative form. 
They merge into one another and, with the exception of the specific 
forms, have no peculiar etiology or pathology. 

Pathological Physiology. — Acute laryngitis may cause considerable 
disturbance of breathing by the swelling of the mucous membrane, and 
in children often leads to spasmodic contraction of the laryngeal muscles, 
with paroxysmal dyspnea (false croup). 

Chronic catarrhal laryngitis may follow the acute form or begin 
gradually. Overuse of the voice and exposure to cold or irritating 
gases or dust are the common causes. The mucous membrane is usually 
thickened and somewhat granular or even papillomatous. There is a 
tendency for the epithelium to assume a squamous or epidermoid char- 



528 



A TEXT-BOOK OF PATHOLOGY 



acter {pachydermia laryngis). In the later stages atrophic changes 
may ensue. Fibrous thickening and stenosis of the larynx sometimes 
result from the chronic irritation of foreign bodies, such as intubation 
tubes. 

Edematous laryngitis is generally known as edema of the larynx. 
Nearly always it is a true inflammatory edema, due to violent irrita- 
tion, general or local infection, or severe local lesions of a chronic nature, 
such as tuberculous or syphilitic ulceration and perichondritis; it is also 
seen in angioneurotic edema. The looser submucous tissues at the 
base of the epiglottis and over the aryepiglottic folds become greatly 
swollen, and the surface is more or less translucent. Sometimes the 
edematous infiltration is yellowish, or even quite purulent, especially 
in cases in which phlegmonous suppurations have extended from neigh- 
boring parts (retropharyngeal abscess, erysipelas). When circumscribed 
areas are affected abscess results. 

Perichondritis, inflammation of the perichondrium of the cartilages 
of the larynx, is usually secondary to serious laryngeal diseases, as 
syphilitic or tuberculous ulcers, carcinoma, etc. It may be primary in 
typhoid fever or other infections. Frequently suppuration and necro- 
sis of the cartilage result, but merely localized induration and swelling 
may occur. 

INFECTIOUS DISEASES 

Diphtheritic and croupous inflammations may be part of the ana- 
tomical changes in diphtheria, but may also occur in typhoid fever, 
scarlet fever, small-pox, or other infectious diseases (due in such cases to 
streptococci or other organisms), or from violent irritation by steam or 
the like. The surface of the larynx is covered with a more or less ad- 
herent grayish or yellowish pseudomembrane, which consists of a net- 
work or masses of fibrin entangling degenerated round cells and epithe- 
lium. The membrane is most adherent where the epithelium is squa- 
mous. Diphtheritic laryngitis usually follows a similar process in the 
pharynx. (See Diphtheria and Pseudomembranous Inflammation, 
Part I, page 131.) 

Tuberculosis is nearly always secondary to pulmonary tubercu- 
losis; primary lesions are exceedingly rare. Small localized tuberculous 
masses or more diffuse tuberculous infiltration are found in the mucosa 
and submucosa, especially on the posterior wall of the larynx, and may 
remain for long periods as the infiltrative type, but caseation and ul- 
ceration are usually early developments (Fig. 225). There is no reason 
to divide the tuberculous lesions in the larynx into different forms, as 
they do not have peculiar courses. Simple catarrhal inflammation or 
hypertrophic conditions of the mucous membrane between the tubercu- 
lous masses, giving rise to warty or polypoid growths or edematous 
laryngitis and perichondritis, may complicate the tuberculous lesions. 
Lupus of the nose and pharynx may extend to the larynx, where it 
occasions nodular thickenings and ulceration. Primary laryngeal lupus 
has been observed. 



DISEASES OF THE RESPIRATORY SYSTEM 



529 



Syphilis may occasion simple catarrh of the larynx, mucous patches, 
or infiltration and erosion of the mucous membrane secondary to 
pharyngeal involvement. The latter 
conditions are most frequent in the 
epiglottis, the posterior wall of the 
larynx, and the vocal cords. Gum- 
mata may occur in the same situ- 
ations independent of pharyngeal 
syphilis, and lead to deeper ulcers. 
In the healing of syphilitic ulcers 
irregular papillomatous elevations 
of the healthy mucosa or extreme 
contractions and deformities of the 
larynx may occur. 

Lepra and glanders sometimes 
occur in the form of nodular swell- 
ings and ulcers. 

Swelling and ulceration, of the 
lymphatic follicles, chiefly at the 
base and side of the epiglottis, anal- 
ogous to the lesions in the intes- 
tines, may occur in typhoid fever; 
and in small-pox there may be small 
areas of infiltration and epithelial 
degeneration, or even pseudomem- 
branes. 

Atrophy of the muCOUS mem- Fig. 225. — Tuberculous erosion and 
hranpq with varinns Hpo-ptwativp ulceration of the larynx, causing extensive 

Dranes wren various aegeneratiye destruction of the vocal cords (from a 

changes Or deposits may OCCUr in specimen in the Museum of the Philadel- 

the larynx as the result of chronic phia Hos P ital )- 

inflammation in loco, or as a part of a constitutional disease (gout, 

rheumatism) . 

Stenosis is due to pressure from without or by contraction of healed 
ulcers. 

TUMORS 

Papilloma. — Over one-half of all tumors of the larynx belong to 
the group of papillomata or papillomatous fibromata. These are simply 
hypertrophied papillae covered with a thick mantle of squamous epi- 
thelium (Fig. 226) . The stroma may be insignificant and the epithelium 
considerable (hard papilloma), or the stroma may be excessive, highly 
vascular, and infiltrated with round cells, while the epithelial covering 
is thin (soft papilloma). Papillomata are most frequent on the false 
vocal cords or on the other parts of the larynx lined with squamous 
epithelium. They usually occur in numbers, but may be solitary. 
Chronic inflammation often determines their occurrence, and they are 
not infrequent around chronic ulcers or carcinoma of the larynx. Simple 
hyperplasia of mucous membrane, of normal structure, occurs in various 
chronic inflammatory conditions of the larynx. 
34 




530 



A TEXT-BOOK OF PATHOLOGY 




Fibroma. — Nodular, sessile, or polypoid fibromata constitute one- 
third of all tumors. They are most frequent 
on the vocal cords and in the upper part of 
the larynx. 

Cystic dilatation of the glands may occa- 
sion mucous polypi. Adenoma, lipoma, myx- 
oma, sarcoma, and chondroma are rare tumors. 
Tumor-like masses of heterotopic thyroid-gland 
tissue have been found in the larynx. 

Carcinoma may be primary or, less fre- 
quently, secondary. Primary carcinoma is usu- 
ally of the squamous variety and occurs about 
the vocal cords. Nodular thickening with 
ulceration results. Papillomatous thickening 
of the mucous membrane frequently surrounds 
the growth. Secondary involvement of the 
cervical glands and esophagus may occur. 

Of 1100 tumors of the larynx collected by 
Bruns, 602 were papillomata; 346, fibromata; 
73, mucous polyps; and 27, cysts; 76 per cent, 
occupied the true cords or the anterior corn- 
Mackenzie found 67 per cent, papillomata and 




Fig. 226.— Papillomata 
of the vocal cords (from a 
specimen in the Museum of 
the Philadelphia Hospital). 



missure of the cords. 
16 per cent, fibromata 



PARASITES AND FOREIGN BODIES 

The larval Trichinella spiralis may infest the laryngeal muscles; 
and lumbricoids occasionally enter from the pharynx. Echinococcus 
cysts are very rare. 

Large foreign bodies may cause death by suffocation. Smaller 
bodies may rest in the larynx, especially the ventricles, for years, be- 
coming surrounded by hyperplastic mucous membrane or a capsule 
of fibrous tissue. Calcareous concretions may form around small 
foreign bodies or spontaneously in the ventricles. 



The Trachea 
malformations 

Congenital Malformations. — Complete absence of the trachea oc- 
curs in acephalic monsters. Congenital decrease in length or diameter, in 
the number or completeness of the cartilages, and similar minor deform- 
ities are more common. An adventitious bronchus is occasionally seen, 
especially on the right side, and fistulous communications with the 
exterior or with the esophagus are rare congenital defects. Diverticula 
may be due to a rudimentary condition of a supernumerary bronchus. 
Congenital cysts may occur between the trachea and esophagus when 
fistulous communications between them become closed at either end. 



DISEASES OF THE RESPIRATORY 



SYSTEM 



531 



Acquired Malformations. — Dilatations of the trachea may be diffuse 
or localized. They depend for their occurrence upon weakness of the 
walls and some impediment to expiration. Saccular dilatations are 
usually on the posterior wall. Narrowing of the lumen may be due to 
pressure of tumors or aneurysms, to new growths or cicatricial contrac- 
tions (especially syphilitic), or to foreign bodies within. 

CIRCULATORY DISTURBANCES 

Anemia and active and passive congestion result from the same 
causes as in the larynx, and the pathological anatomy is the same. 

INFLAMMATIONS 

Inflammations are usually associated with laryngitis or bronchitis, 
and are due to the same causes. Simple catarrhal and pseudomem- 
branous inflammations are met with. Foreign bodies may cause exten- 
sive and deep inflammation, leading to ulceration and sometimes per- 
foration. Chronic inflammation assumes a proliferative and, later, an 
atrophic character. Proliferative (polypoid) inflammation is not infre- 
quent after tracheotomy, and may occasion serious obstruction. Ozena 
of the trachea may be associated with nasal ozena. 

INFECTIOUS DISEASES 

Tuberculosis and syphilis occur under the same circumstances as 
in the larynx. Syphilis may, however, affect the trachea and bronchi 
independent of disease of the pharynx or larynx. 

TUMORS 

Primary tumors are rare. Secondary involvement by cancer, ex- 
tending from the esophagus or thyroid gland, or by sarcoma, from the 
surrounding lymphatic structures or thymus gland, is more frequent. 
Ecchondroses and osteomata may spring from the cartilages, and 
multiple chondromata have been found in the mucous membrane. 
Retention-cysts of the mucous glands are occasionally seen on the 
posterior wall, protruding outside the trachea. 

The Bronchi 

Anatomical Considerations. — The larger bronchi correspond very 
closely to the trachea in structure. The smaller divisions have thinner 
walls, being less provided with cartilaginous rings, but having instead 
small cartilage-plates and a greater abundance of muscle-fibers. The 
tubes having a diameter less than 1 mm. are called the terminal bron- 
chioles, and lead into yet smaller tubes, the alveolar passages, which open 
into dilated infundibula, and the last named are finally surrounded by 



532 



A TEXT-BOOK OF PATHOLOGY 



air-sacs. The lining epithelium is stratified columnar ciliated down to 
the terminal bronchioles, where it becomes simple columnar. In the 
alveolar passages there is first polygonal, then flat, epithelium; while 
in the infundibula and air-sacs there are practically only flat epithelial 
cells. 

CONGENITAL MALFORMATIONS 

These are rare and unimportant. Dilatations or narrowing and 
anomalous division of the tubes have been noted. (See Trachea.) 

CIRCULATORY DISTURBANCES 

Anemia and hyperemia occur under the same circumstances as in 
the trachea and larynx. 

Hemorrhage. — Intense congestion may occasion hemorrhages into 
the mucous membrane or into the bronchi themselves. More fre- 
quently hemorrhage is due to catarrhal inflammation, tuberculous 
ulceration, or a general hemorrhagic tendency. Aneurysms of the 
aorta (see Fig. 220) and the small aneurysms of the pulmonary arterioles 
in tuberculosis of the lungs not infrequently rupture through the 
bronchi. 

INFLAMMATIONS 

Both acute and chronic bronchitis are common conditions, and there 
are several forms. 

Acute catarrhal bronchitis results from exposure, from inhalation 
of irritating gases, and from downward extension of tracheal catarrhs. 
The terminal bronchioles are frequently affected secondarily in pul- 
monary diseases. Bronchitis is constantly associated with some of the 
infectious fevers — typhoid fever, measles, whooping-cough, etc. Various 
micro-organisms have been found in bronchitis. Among these are the 
pyogenic micrococci, the diplococcus of Frankel, the bacillus of Fried- 
lander, the Bacillus influenzae, the B. coli, with many others. The 
mucous membrane presents an intensely red color; at first it is dry, 
but later a mucous or mucopurulent exudate is formed (see Fig. 32). 
The exudation may be excessive in quantity, in which case the condition 
is called bronchorrhea. This may be serous or purulent, and is sometimes 
very offensive in odor (fetid bronchitis). 

Accordingly, as the exudate assumes a serous, mucous or mucopuru- 
lent, or fibrinous character, these names are applied. They have no 
etiological significance aside from the specific infections. All forms may 
go over into gangrenous bronchitis by retention and putrefaction of 
exudate. 

Microscopically, the bronchial mucous membrane is infiltrated with 
round cells, especially in the purulent cases; the epithelial cells are de- 
generated, many being converted into goblet-cells; and the mucous 
glands are distended with mucus. The mucosa of the bronchi is covered 
with mucopurulent material containing degenerated epithelial cells and 



DISEASES OF THE RESPIRATORY SYSTEM 



533 



detritus. The inflammatory conditions may extend outward as far as 
the peribronchial tissue, and occasionally there is some perichondritis. 

Capillary bronchitis is a form confined, at least in the early stages, 
to the finest bronchioles, and it may go over into a catarrhal pneumo- 
nitis. 

Pathological Physiology. — Bronchitis may occasion no other dis- 
turbance than cough. In many cases, however, the infection may cause 
fever and general depression. Substernal soreness or pain is not infre- 
quent, while generalized thoracic pain may result from the violent 
coughing. Dyspnea is rare excepting in children and old persons, in 
whom cardiac weakness and spasmodic contractions of the bronchi 
seem to be operative. 

Chronic catarrhal bronchitis occurs after repeated attacks of the 
acute form, and especially in old persons or in those who have some 
cardiac weakness which tends to cause congestion of the bronchi. 
Gout seems to constitute a dis- 
tinctly predisposing cause. Chronic 
bronchitis is frequently associated 
with chronic diseases of the lungs. 
In chronic cases the mucous mem- 
brane may undergo considerable 
alteration. Frequently the ciliated 
cells disappear entirely and are re- 
placed by columnar or polygonal 
epithelium; and hypertrophic con- 
ditions of the mucous membrane 
are sometimes present. More fre- 
quently the bronchus is uniformly 
thickened by cellular infiltration 
and overgrowth of fibrous tissue. 
It may, indeed, become hypertro- 
phic, and when the overgrowth en- 
croaches upon the lumen with pro- 
gressive granulation tissue an ob- 
literating bronchitis occurs. The 
exudate in chronic bronchitis is purulent and is accompanied by dis- 
arrangement and alterations in the bronchial epithelia. 

Fibrinous bronchitis occurs under a variety of conditions. It is most 
frequent in association with laryngeal and tracheal diphtheria, but may 
also be due to inhalation of powerful irritants. Fibrinous inflammation 
of the finer bronchi occurs in both croupous and catarrhal pneumonia. 
Finally, there is a form of chronic or essential fibrinous bronchitis, 
characterized by periodic attacks, in which fibrinous casts of the 
bronchi are formed and discharged (Fig. 227). In all forms of fibrinous 
bronchitis there are often found in the sputa, on microscopical examina- 
tion, fine spirals wound about a central fiber (Curschmann's spirals); 
and within these or associated with them the small octahedral crystals 
described by Charcot and Leyden (Fig. 228). 




Fig. 227. — Large bronchial coagulum; 
chronic fibrinous bronchitis (Vierordt). 



534 



A TEXT-BOOK OF PATHOLOGY 



Bronchiolitis Exudativa. — This term was given by Curschmann 
to the condition of the terminal bonchioles he assumed to be present in 
cases of asthma. The sputa contain the spirals that bear his name and 
Charcot-Leyden crystals. The sputa in these cases are further char- 
acterized by the abundance of eosinophile cells (Figs. 228 and 229). 




Fig. 228. — Sputum from a case of asth- 
ma, showing Curschmann spirals, Charcot- 
Leyden crystals, leukocytes, and numerous 
free eosinophile granules; unstained speci- 
men (Jakob). 




Fig. 229. — Sputum from a case of asthma, 
showing leukocytes, some containing eosino- 
phile granules, free eosinophile granules, 
and micrococci; stained with eosin and 
methylene-blue (Jakob) . 



Ulcers of the bronchi are met with in severe catarrhal inflammations, 
but more frequently are tuberculous, syphilitic, or due to extension of 
ulcerative processes from neighboring parts. It is not unusual to find 
ulceration in the main bronchus opposite the point of pressure of an 
aneurysm. 

Peribronchitis may occur from direct extension of inflammation from 
within, or it may be due to extension along the lymphatic channels from 
the pleura or interlobular septa of the lung. It is found most frequently 
as a part of pulmonary tuberculosis, and may be fibrous, caseous, or 
purulent. 

STENOSIS AND OBSTRUCTION OF THE BRONCHI 

The smaller bronchial tubes may be considerably occluded by 
catarrhal swelling of the mucosa and accumulation of exudate within. 
Clinically, this is often so marked in bronchitis affecting the terminal 
bronchioles as to have suggested the name "suffocative catarrh." (This 
capillary bronchitis is always merely a part of bronchopneumonia, and 
will be considered under that head.) More serious obstructions of the 
bronchi occur when old ulcers have healed, leaving cicatrices; or in 
cases of tumors of the bronchi or pressure upon the outside. If the ob- 
struction be total and permanent, atalectasis of the lung occurs in that 
part supplied by the affected tubes. In temporary obstruction a mild 



DISEASES OF THE RESPIRATORY SYSTEM 



535 



local emphysema occurs beyond the obstruction. Foreign bodies are 
usually coughed up, but may remain for long periods and occasion ob- 
struction. 

BRONCHIECTASIS, OR DILATATION OF THE BRONCHI 

This is due to increased pressure within the bronchi or to some 
weakness of the walls, or to both, when the fault lies primarily in the 
bronchial walls. The weakening of the walls is most frequently due to 
chronic bronchitis. If it is extreme, simply the force of the inspired air 
may suffice to cause dilatation, but the increased expiratory efforts of 
coughing may aid materially. When a part of the lung is collapsed 
(atelectasis) the impediment to the entrance of air leads to dilatations 
of the bronchi above the collapsed area. This is especially noted in 
children. The weight of accumulating secretions in the tubes is an occa- 
sional cause of bronchiectasis. Finally, in fibrous pneumonia the trac- 
tion of the connective tissue, attaching itself, on the one hand, to the 
outer wall of the bronchus, and, on the other hand, to the pleura, may 
bring about considerable dilatations. 

An analysis of series of cases shows that chronic bronchitis and 
chronic cough stand at the head of the etiological antecedents. Probably 
in a much larger proportion of cases than is now recognized there is an 
association of bronchial dilatation with chronic bronchitis. The clini- 
cian and pathologist also have in the past given little attention to cases 
in which the dilatations were not pronounced or saccular. Clinically, 
there can, however, be recognized a group of cases of chronic bronchitis 
with excessive sputa in which the bronchi are probably uniformly 
though slightly dilated. 

Among the other causes tabulated ° b 

are preceding pneumonia, pleurisy, 
tumor, foreign body in the bronchus, 
aneurysm. 

A congenital varicose dilatation 
of bronchi is sometimes seen. 

The enlargement of the bronchus 
may be localized, when it is termed 
saccular bronchiectasis; or more uni- 
form, when the names cylindrical 
and fusiform are applied, accord- 
ing tr> thp shfmp of thp hrnnphiis Fig. 230.— Bronchiectasis: a, Saccu- 

mg to tne snape or tne oronenus lar; b ^ cylindrica i ; ne-haif natural size 
(Fig. 230). The mucous mem- (Orth). 
brane may be almost normal in ap- 
pearance in small dilatations, but more commonly is thickened and 
irregular on the surface. There may even be actual polypoid out- 
growths, and ulcerations may occur when the secretions are specially 
abundant and irritating. Microscopically, the epithelium is found to 
approach the squamous type; the wall of the bronchus is generally 
infiltrated and cirrhotic. The exudation is generally purulent and 
copious, and may be very fetid. Occasionally it is thick and cheesy. 





536 



A TEXT-BOOK OF PATHOLOGY 



Bronchiolectasis. — Cases of extensive dilatation of the small 
bronchi and bronchioles have been observed. They are especially com- 
mon in childhood and may be of a bronchitic type when bronchitis is 
the precedent condition, and an obscure pneumonic form in which the 
bronchiolar dilatation is associated with pneumonic consolidation. 




Fig. 231. — Honey-comb lung, illustrating the extreme results of generalized acute bron- 
chiolectasis of the bronchitic type (H. Morley Fletcher's case). 

Bronchiolitis may be acute or chronic in its course and localized or 
quite general. In some cases the lung is quite honey-combed in appear- 
ance (Fig. 231). 

INFECTIOUS DISEASES 

Tuberculosis of the bronchi is usually associated with pulmonary 
tuberculosis, and appears in the form of miliary or larger nodules 
in the mucosa or submucosa, which tend to break down to form ulcers. 

Syphilis sometimes occurs in the form of eruptions and ulcers. There 
may be dense scar formation and deformity in consequence of the 
healing of such ulcers. 

TUMORS 

Polypoid conditions of the mucosa occur in cases of chronic bronchi- 
tis. Fibroma, chondroma, and lipoma are rare forms of tumors. Pri- 



DISEASES OF THE RESPIRATORY SYSTEM 537 

mary cancers may spring from the mucous glands or from the surface 
epithelium, but are very rare. Leukemic nodules are seen in the bronchi 
at times, and lymphosarcomata are not rarely found to spring from the 
peribronchial lymphatic tissues. 

PARASITES AND FOREIGN BODIES 

Bronchiectatic cavities may contain a growth of aspergillus — 
mycosis aspergillina. Round worms may enter by migration, and 
hydatid cysts are met with. The Paragonimus westermanii is a rare 
parasite invading the bronchi. 

Foreign bodies from the exterior usually enter the right bronchus. 
They often lead to serious inflammation and suppuration, unless they 
are coughed up. Bronchial concretions sometimes form by inspissa- 
tion of the secretions, especially in bronchiectatic cavities. Very rarely 
cartilaginous or bony masses, derived by outgrowth and later separa- 
tion from the bronchial cartilages, are observed. 

The Lungs 

Anatomical Considerations. — The structure of the lungs in their 
unexpanded condition is very similar to that of an epithelial gland, 
consisting of ducts, the bronchi; and glandular tissue, the pulmonary 
parenchyma. The terminal bronchioles divide into several alveolar 
passages, which open into infundibula, and these, in turn, are surrounded 
by air-sacs. The groups of infundibula connected with a terminal bron- 
chiole constitute an acinus. Neighboring acini unite to form lobules, 
and the lobules unite to form lobes. The epithelial lining cells of the air- 
sacs are large flat plates, which resemble endothelial cells very closely. 
Beneath these cells is a layer of elastic tissue, which gives the lungs 
their characteristic elasticity, and 'in which is embedded a rich net- 
work of capillaries, that carry on the proper respiratory function of 
the lungs. These capillaries are the terminal ends of the pulmonary 
artery. Another set of blood-vessels, the bronchial arteries, serve only 
to nourish the walls of the bronchi and the structure of the lungs them- 
selves. The return circulation is mainly carried on by the pulmonary 
veins, which receive the blood of the pulmonary arteries and much of 
that of the bronchial arteries. The distribution of the lymphatic ves- 
sels in the lungs is of the greatest significance in pathological anatomy, 
especially with regard to the dissemination of infectious diseases in the 
lung itself. One system of lymphatics begins in the lymph-spaces be- 
tween the cells of the intervesicular septa. These lymph-spaces deliver 
their contents to lymphatic capillaries in the same region, and these, in 
turn, follow the alveolar passages, surrounding the latter on all sides. 
Where the several alveolar passages unite to form a terminal bronchiole 
the smaller lymphatic capillaries also unite to form larger branches, 
which follow the bronchioles. Other lymphatic vessels surround the 
pulmonary veins, constituting a perivascular system. Still another 



538 



A TEXT-BOOK OF PATHOLOGY 



system begins in small subpleural capillaries, which unite, enlarge, and 
then penetrate the lung along the interlobular septa. Some of them, 
however, pass at once to the peribronchial and perivesicular tissues. All 
the lymphatic trunks leave the lung at the root and eventually discharge 
into the thoracic duct. 

Collections of lymphoid cells are found in various places along the 
lymphatics in the tissue of the lung. Near the root these are of consider- 
able size, and merit the name of lymphatic nodes or glands. Still 
larger and more important ones are found surrounding the bronchi just 
outside the lungs and around the end of the trachea. 

CONGENITAL DEFECTS 

Complete absence of the lungs has been noted in certain monsters. 
One lung may be absent, or its parenchyma may be undeveloped, 
while the bronchi are dilated even to a cystic condition. The opposite 
lung is compensatorily enlarged. Minor abnormalities in the division 
of the lobes and the like are not rare; and in a few instances accessory 
lobes, wholly disconnected from the rest of the lung, have been observed. 

CIRCULATORY DISTURBANCES 

Anemia of the lung occurs as a part of general anemia, from pres- 
sure upon the lung, or from obstruction or obliteration of the blood- 
vessels. The last is the cause of the great pulmonary anemia in emphy- 
sema of the lungs. The lungs are pale in color or of a mottled appear- 
ance in elderly persons, in whose organs considerable pigment is usually 
present. The apex is the first part to show anemia. 

Active Hyperemia or Congestion. — Exercise constantly leads to in- 
creased flow of blood to the lungs, and this may be extreme, causing rapid 
death (apoplexia pulmonum vascularis). In cases of irritation of the 
lungs by the inhalation of heated or cold air, or of irritating gases, and 
in certain lesions of the base of the brain there may be more or less 
active congestion of the lungs (Fig. 232). Collateral hyperemia occurs 
when the opposite lung or some other part of the body becomes anemic 
through a stoppage of the circulation in that part. The lung in active 
hyperemia has a dark-red color, and on section blood flows from the 
surface of section. The alveoli may contain free blood, and in marked 
cases there is blood in the sputa during life. 

Passive hyperemia is, for the most part, a chronic condition due to 
causes which prevent the outflow of blood from the lungs. The most 
frequent cause is valvular disease, particularly mitral stenosis and re- 
gurgitation; but weakness of the left ventricle from fatty disease or 
fibroid degeneration acts in a similar manner. Any local cause of hin- 
drance to the outflow of the blood in the veins leads to similar passive 
congestion. It is often found in the dependent parts of the lungs in 
cases of great asthenia, as in typhoid fever, when the respiratory 
movements are ineffectual in properly emptying the pulmonary vessels. 



DISEASES OF THE RESPIRATORY SYSTEM 539 

This is called hypostatic congestion; not infrequently it leads to hypo- 
static pneumonia when irritants are inspired or descend through the 
bronchi to the parts of the lung affected. Postmortem there is often 
a similar hypostatic congestion, but without any evidences of catarrhal 




Fig. 232. — Acute congestion of the lung (Karg and Schmorl). 

inflammation of the bronchi, such as always occurs in the cases de- 
veloped during life. 

The lung in passive hyperemia is dark-red in color and heavy. In 
the more acute cases it is moist on section, being infiltrated with serous 




Fig. 233. — Phagocytic cells of the sputum, containing blood-pigment, from a case of 
cardiac congestion of the lungs (Jakob) . 

exudate and blood; in chronic cases, as in slow heart-failure, the tissue 
is dry and indurated. Microscopically, the blood-vessels in the alveolar 
walls are seen to be greatly distended, irregular, tortuous, and project 
into the alveoli. Red and white blood-corpuscles are seen within 



540 



A TEXT-BOOK OF PATHOLOGY 



the alveoli and in the interstitial tissues. In the later stages the red 
corpuscles either re-enter the circulation or break down to form dark 
pigment-granules within the alveolar epithelial cells, the leukocytes, or 
lying free in the tissues of the alveolar walls. In such cases there are 
at the same time considerable hyperplasia and induration of the con- 
nective tissue of the lung; and the whole process is called cyanotic 
induration. In cases of heart disease with congestion of the lungs there 
are very commonly found in the sputa pigmented epithelial cells and 
leukocytes, such as those described above (Fig. 233). These have been 
called heart-failure cells (Herzf ehlerzellen) . They are of some diagnostic 
importance. 

Edema occurs most frequently as a result of passive hyperemia 
and is due to disproportion in the expulsive force of the two ventricles. 
The acute edema of nephritis may possibly be due to the inability of the 
left heart to empty because of the continued circulatory hypertension. 
In other cases the edema is the consequence of general septic condi- 
tions which lead to unusual permeability of the blood-vessels. In this 
group of cases belong the instances of "acute idiopathic edema" which 
are apparently independent of cardiac weakness and probably depend- 
ent on some form of infection. This is sometimes seen as an acute fatal 
attack in persons suffering from vascular disease, especially of the 
aorta, and in nephritics. Similar edema, not dependent on passive 
congestion, occurs in the parts of the lung surrounding inflammatory 
areas, and in some cases sudden pulmonary edema seems dependent on 
vasomotor relaxation. In cases of stenosis of the larynx, edema of the 
lung may result from the reduced pressure of air in the alveoli and the 
consequent suction of blood to the pulmonary circulation. In the cases 
of edema due to passive congestion the lungs are dark-red in color, 
firmer than normal, pit on pressure, do not show normal crepitation, 
and on section more or less serous fluid, rendered frothy by admixture 
of air, exudes from the cut surface. In long-standing cases the exuding 
fluid may be dark by admixture of degenerated blood. In the other 
forms of edema the lung may be quite light in color, generally grayish, 
but on section the same frothy serum exudes from the surface. 

Microscopically, little is to be seen. There is some congestion of the 
septa, with a few epithelial cells and a hyaline coagulum in the alveoli. 

Hemorrhage. — Small punctate hemorrhages occur in cases of severe 
congestion or inflammation, in the hemorrhagic or infectious diseases, 
and in consequence of high blood-pressure, as in death from asphyxia or 
in whooping-cough. The cause of such hemorrhages is inflammatory or 
degenerative weakening of the vessel walls or an obstruction of the lumen. 
When the former exists, and the latter supervenes, the production of hem- 
orrhage is easier and more extensive. When hemorrhage from congestion 
is combined with serous effusion the lung assumes an appearance not 
unlike that of a hyperemic spleen (splenization) . A form of apparent hem- 
orrhage is seen in cases in which the blood is aspirated from the bronchi. 
In such cases lobular spots of hemorrhagic infiltration are found at the 
bases. Large hemorrhages into the substance of the lungs may be 



DISEASES OF THE RESPIRATORY SYSTEM 



541 



traumatic, or they may be due to rupture of an adjacent aneurysm into 
the lung. Small or large pulmonary hemorrhages are at times due to 
lesions of the nervous system, especially of the base of the brain. 

Hemorrhage from the lungs, discharging externally through the 
bronchial tubes, is most commonly due to tuberculosis, and is particu- 
larly frequent in the late stages, when cavities have formed. The im- 
mediate source of the bleeding is generally an eroded vessel in the wall 
of the cavity, and a small miliary aneurysm is commonly found at the 
point of erosion. Hemoptysis may be the first indication of the existence 
of pulmonary tuberculosis, but the old belief that hemorrhages cause 
phthisis is ill founded. A hemorrhage or any other lesion of the lungs 
may, of course, add to the liability to infection ; but, as a rule, the cases 
in question are instances of hemorrhage occurring before the other 
evidences of the pulmonary disease have become marked. Occasionally, 
hemoptysis is due to congestion of the lungs, to erosion of small blood- 
vessels from gangrene, abscess or the like, or to vicarious menstruation. 

Hemorrhagic infarcts may occur in the lungs, as in other places, 
from obstruction of the arteries by emboli. The latter come from the 
right heart or from the general venous system, and lodge in the smaller 
branches of the pulmonary artery, frequently at their points of sub- 
division. Very often, however, emboli are not found, or, if so, are so 
small as to have been unable to cause obstruction without the associated 
thrombosis, or there may be purely thrombotic occlusion. Valvular 
lesions and muscular weakness of the heart aid greatly in the produc- 
tion of infarctions by causing a sluggish circulation in the pulmonary 
vessels, and thus encouraging thrombosis. Infarctions are occasionally 
due to thrombosis of the pulmonary veins without obstruction of the 
arteries ; more rarely they are caused by occlusion of one of the bronchial 
tubes. The latter condition leads to collapse (atelectasis) of the part of 
the lung associated with that tube, to consequent congestion (see Ate- 
lectasis), and, sometimes, when the congestion is severe, to hemorrhage. 
In addition, it is to be remembered that hemorrhages into the lungs 
are likely to have the shape and appearances of ordinary infarcts, be- 
cause they occupy the area supplied by the bronchus into which the blood 
finds its way. Contributory causes are to be found in emphysematous 
lungs or those with senile or chronically altered arteries. These act as 
conditions favoring embolism and, secondarily, thrombosis by reason of 
degenerated vessel walls, and a loss of accommodative power by the 
pulmonary vascular and tissue tension. Infarctions are most frequently 
found in the lower lobes and in the right lung; they are usually multiple 
(Fig. 234) and have the characteristic wedge shape, the base of the 
wedge directed toward the pleural surface. They are hard, airless, dark 
colored, and project above the other parts on section and on the pleural 
surface. The pleural surface is at first shining and dry; later it becomes 
moist, then cloudy, and a layer of lymph appears, sometimes to be fol- 
lowed by a distinct fibrinous or adhesive pleuritis. Microscopically, 
there is seen a uniform hemorrhagic infiltration of the tissues (Fig. 235) 
and not infrequently hyaline thrombosis of the smaller blood-vessels. 



542 



A TEXT-BOOK OF PATHOLOGY 



Toward the apex of the infarct there is more fibrin in the blood-vessels, 
and the main vessel may be found obstructed by an embolus or throm- 
bus. Small infarcts may be wholly removed through the vascular and 
lymphatic channels after liquefaction and granular degeneration of the 




Fig. 234. — Double hemorrhagic infarct of lung (from a specimen in the collection of 

Dr. Allen J. Smith). 

blood-clot. More commonly a pigmented scar is left. Softening and 
cyst formation may occur, or in cases in which the original embolus 
was infected by micro-organisms, or in which the infarct becomes in- 
fected through the bronchial tubes, abscess or gangrene may result. 




Fig. 235. — Hemorrhagic infarctioD of the lung (from a photograph by Dr. Wm. M. Gray). 

Embolism without infarction is not infrequent in the lungs. An 
interesting form is fat-embolism, resulting from fracture of a bone 
with disorganization of the marrow, and less frequently from traumatic 
disturbances of other fat tissues. When large branches of the pulmonary 



DISEASES OF THE RESPIRATORY SYSTEM 



543 



artery are occluded in this way, or when numerous vessels are ob- 
structed, sudden death may result. In other cases there are merely 
great dyspnea and oppression. Air-embolism, embolism of hydatid 
cysts and of portions of tumors are rare. Attention has been called to 
the embolism of placental cells in certain cases of eclampsia. 

HYPERTROPHY AND ATROPHY 

Hypertrophy. — True hypertrophy, in the sense of increase of all the 
constituents of the lung tissue, is extremely rare, and probably only 
occurs when areas of the pulmonary tissue have been rendered useless 
early in infancy or in fetal life. Cases have been observed, however, 
in which a single lung occupied the entire side of the thorax to which it 
belonged, and also a part of the other side, where complete atrophy of 
the other lung had existed. It may be that limited areas of hyper- 
trophy occur more frequently than we at present believe, but evidence 
is wanting. 

Partial Hypertrophy. — The muscular tissue of the intervesicular 
septa and of the smaller bronchioles not infrequently undergoes pro- 
liferation or hyperplasia when there has been obstruction in the air- 
passages, so that greater expiratory force was required. Similarly, the 
elastic tissues may become increased ; but these are not instances of true 
hypertrophy. 

Atrophy. — Aside from that which occurs as a part of emphysema, 
atrophy does not take place. 

EMPHYSEMA 

By this term is indicated an increase of the air contained within 
the lungs, either in the normal tubes and_alyeoli or in the interstitial 
connective tissue. Two varieties of emphysema may be distinguished 
by their essentially different nature. These are the interstitial and the 
vesicular. 

Interstitial emphysema of the lungs is similar to the emphysema 
of the subcutaneous tissues — i. e., the term refers to the existence of air 
within the fibrous tissue of the lung. This occurs in the course of affec- 
tions in which there is some obstruction to the expiration, combined with 
severe coughing or forcible expiratory efforts, leading to rupture of the 
intervesicular septa and extravasation of air. Degenerative or in- 
flammatory weakness of any part of the pulmonary structure would, of 
course, act as a primary cause. Interstitial emphysema is most com- 
monly observed in such diseases as whooping-cough and membranous 
croup; it may also result simply from straining efforts, as in women 
during labor, or from forcibly blowing wind-instruments, etc. The air 
from the ruptured air-vesicle finds its way into the interalveolar and in- 
tervesicular septa, and, passing along these, eventually reaches the inter- 
lobular and subpleural connective tissue, where it is seen in the form of 
small blebs, movable from place to place. The process may extend to 



544 



A TEXT-BOOK OF PATHOLOGY 



the roots of the lungs, and even to the mediastinal tissues or to the sub- 
cutaneous tissues of the neck. When an air-vesicle near the pleural 
surface ruptures, pneumothorax may result. 

Vesicular emphysema is the term used to designate overdistention 
of the alveoli and air-sacs of the lung. Two factors play a part in the 
causation of this condition : first, increase of the pressure under which the 
air exists in the lung; and, second, degenerative or inflammatory 
weakness, with loss of elasticity of the lung structure itself. There are 
several varieties, and the causes vary somewhat in each. 

(a) Acute vesicular emphysema results simply from excessive air- 
pressure within the alveoli, and may be more or less widespread. It 
occurs in eases in which inflammatory swelling or mucous secretions 
within the bronchi obstruct the expiration of air, but are not sufficient 
to impede the more vigorous inspiratory force. There results over- 
distention of the alveoli and air-vesicles. Somewhat similar conditions 
are present when the entrance of air into certain parts is impeded by 
obstruction or disease of the bronchi or by consolidations of the pul- 
monary tissue. Localized emphysema of other parts results (see Fig. 237) ; 
the term vicarious emphysema is applied to such cases. This is not 
unusual in the lobules of the lung surrounding areas of pneumonic or 
tuberculous consolidation, and may affect an entire lobe or lung when 
the entrance of air into the other lobes or the other lung is prevented 
(compensatory emphysema). 

Pathological Anatomy. — In these cases of acute and vicarious 
emphysema there is simply overdistention of the alveoli, and the tissue 
presents a paler color than normal and a cotton-like sensation when 
grasped in the fingers. Microscopically, nothing beyond overstretching 
of the septa and some anemia of the vessels is apparent. If the causes 
continue to operate, changes similar to those found in chronic vesicular 
emphysema ensue. 

(b) Chronic vesicular emphysema is the ordinary form of emphy- 
sema, and is sometimes spoken of as substantial emphysema. 

Etiology. — Chronic vesicular emphysema commonly occurs in 
elderly persons, and is predisposed to by attacks of bronchopneumonia 
and by the existence of other inflammatory and congestive conditions 
of the lungs. These conditions lead to weakness or loss of elastic tissue 
in the lungs. Heredity plays a part in the same direction, and it is 
supposed by some that there is an abnormal lack of development of the 
elastic tissue in the lungs of such persons, rendering them more sus- 
ceptible to this disease. The direct exciting cause of emphysema is 
increase of the air-pressure within the alveoli, and much speculation 
has been indulged in to discover whether inspiration or expiration 
plays the more important part in increasing the pressure. It seems likely 
that the expiratory force is the more important one, as in the case of 
constant coughing in chronic bronchitis, the blowing of wind-instru- 
ments, and the constant straining in certain pelvic disorders, all of 
which may lead to emphysema. Unusual rigidity of the chest walls, as 
in abnormal ossification of the costal cartilages, is held responsible for 



DISEASES OF THE RESPIRATORY SYSTEM 



545 



some cases, the extra force necessary to expand the vesicles being 
answerable for their dilatation. 

Pathological Anatomy. — The lung increases in size, and very often 
remains distended when the thorax is opened postmortem. The edges 
are rounded; the organ is light in color, and has a cotton-like feeling 
when squeezed between the fingers. On section into it the alveoli may 
be seen to be distended, and there may be cavities of quite considerable 
size, often as large as a pea, and sometimes even that of a cherry or 
plum (Fig. 236). Large spaces of this kind are not unusual near the 
pleural surface; the term bullous emphysema has been used in reference 
to such cases. The pigment matter of the lung is very much lessened, 
and may be distributed in radiating or parallel lines. This lessening 
of the pigment is not alone due to its distribution over a greater space, 
but there is also actual disappearance by removal through the lymphatic 
channels and through expectoration. 




Fig. 236. — Emphysema of the lungs (Karg and Schmorl). 

Chronic emphysema may be a general process affecting all parts 
of both lungs, or it may be localized. In the latter case it is the apex 
and anterior edges that are most commonly involved, but spots of 
emphysema may be seen here and there in other parts of the lung, 
interspersed with normal tissue. The involvement of the apex and an- 
terior portions is due to the fact that the expiratory force is more apt to 
distend these portions of the lung than the lateral and basal portions, 
which receive the uniform support of the sides of the chest and the 
diaphragm as these contract against the lung. 

Microscopically, emphysema is found to consist in enlargement of 
the vesicles and alveoli by distention and by atrophy and disappear- 
ance of the intervesicular and interalveolar septa {atrophic emphysema) . 
Studied from the earliest stage, there will be found, first, overdistention 
of the air-sacs, then a gradual thinning, and finally vacuolization of the 
intervesicular septa at their thinnest parts. Coincidentally, the small 

35 



546 



A TEXT-BOOK OF PATHOLOGY 



capillaries are compressed, and are finally converted into hyaline cords. 
The anemia consequent upon this determines additional atrophy and 
degeneration of the septa and fatty degeneration of the loosened epi- 
thelium, so that eventually the whole of the septum disappears. Later, 
adjacent alveoli intercommunicate and large spaces are thus formed. 

The obstruction to the pulmonary circulation due to the obliteration 
of the capillaries leads to collateral hyperemia of the larger branches 
supplying the bronchi, and thus prolongs the chronic bronchitis, which 
in the first instance may have been the cause of the emphysema. Sub- 
sequently, collateral anastomosis between the pulmonary arteries and 
the bronchial system of blood-vessels is established. 

Associated Conditions in Other Organs. — The shape of the thorax 
in emphysema is characteristic. The chest is in a constant state of ex- 
treme inspiration, the clavicles elevated, the sternum protruded, the 
back arched. It has a shape well likened to that of a barrel. The dia- 
phragm is usually depressed and the liver is below its normal position; 
the heart is almost or completely covered over in front and usually 
pressed somewhat backward from the chest wall. 

Pathological Physiology. — The effect of emphysema upon the circu- 
lation is important. The obstruction of the pulmonary capillaries leads 
to increase of pulmonary pressure, and eventually hypertrophy of the 
right heart; later, dilatation of the right ventricle ensues, and character- 
istic cardiac dropsy with general cyanosis may result. 

(c) Senile emphysema is due to thinning of the intervesicular 
septa, the result of the atrophic processes to which old age predisposes. 
There is not necessarily any element of increased air-pressure in the 
causation of this form of emphysema, and the volume of the lung 
may not be notably increased, though the tissue is lighter and the air- 
spaces are found to be increased. The lung is light in color and often 
collapses readily. 

ATELECTASIS 

The term "atelectasis" is applied to two distinct conditions, one 
occurring as a congenital affection, in which the lung has never been 
properly expanded by air; the other occurring in after life, in which the 
lung is compressed or collapsed, so that the alveoli and air-vesicles are 
rendered airless. 

Congenital atelectasis is found in newborn babes in whom the 
inspiratory power has been so deficient, as the result of general weakness 
or compression of the thorax, or of compression of the brain by cerebral 
hemorrhage, that the lungs, or parts of them, have never been expanded. 
It may also take place in a purely mechanical way by obstruction to the 
air-passages by meconium or other foreign matter. 

Pathological Anatomy. — Congenital atelectasis commonly affects 
the bases and posterior portions of the lung. The area of disease is of a 
dark reddish color; it is rather tough, and on section presents a smooth 
appearance; pressure gives no sign of crepitation. If a portion be thrown 
into water, it sinks. Usually a considerable part of the lung is involved, 



DISEASES OF THE RESPIRATORY SYSTEM 



547 



but sometimes merely lobular areas are affected. By inserting a blow- 
pipe into the bronchi the lung may be inflated, and resumes its normal 
appearance, provided the condition has not persisted for any length of 
time. If the child does not perish, secondary changes take place. 
The epithelium of the alveoli degenerates, more or less proliferation of the 
connective tissues of the septa occurs, and the pleura over the diseased 
area is prone to become thickened. The atelectatic portion of the lung 
in such cases remains collapsed; it is smooth on section, free of pigment, 
and can no longer be inflated. Secondary dilatation of the bronchioles 
and bronchi may ensue. 

It is of interest, in a medicolegal 
sense, to recognize that atelectasis re- 
sembling the congenital form may be 
met with in the bodies of infants that 
have lived, breathed, and even cried 
lustily. The explanation of this is that 
collapse occurs some time after birth, 
and, that as the lung has practically still 
its fetal characteristics, the resulting 
atelectasis is the exact counterpart of 
the congenital form. 

Atelectasis in later life occurs under 
a variety of conditions. It may simply 
be the result of compression of the lung 
by pleural effusions, by deformities of 
the chest, by tumors, aneurysms, and the 
like. It may also be met with in cases in 
which the bronchial tubes have become 
obstructed. The larger bronchi may 
be occluded by the pressure of tumors 

or aneurysms, or by foreign bodies, and the resulting atelectasis is of 
considerable extent; the smaller bronchi and bronchioles are frequently 
obstructed by intense catarrhal thickening of their mucosa, and in con- 
sequence lobular areas of atelectasis are developed. The latter is espe- 
cially frequent as one of the pathological features of bronchopneumonia 
(q. v.). 

The explanation of atelectasis as the result of bronchial obstruction 
has occasioned much discussion, and several theories have been pro- 
posed. In some cases it is not unlikely that mucous secretions within 
the bronchi may prevent inspiratory entrance of air into the lungs with- 
out opposing any obstacle to expiration, so that collapse is gradually de- 
veloped. In other cases it is likely that both inspiration and expiration 
are prevented, while the air contained within the air-vesicles is gradu- 
ally absorbed. It is claimed that first the oxygen, later the carbonic 
acid, and finally the nitrogen are absorbed; the collapse of the alveoli 
then becomes complete. It is possible, also, that atelectasis may be 
developed as the result of the failure of respiratory motions on one side, 
or affecting a certain part of the lung. As a result of this, the elasticity 




Fig. 237. — Atelectasis due to 
bronchial obstruction: acute em- 
physema of the unaffected portions 
of the lung (Orth). ■ 



548 



A TEXT-BOOK OF PATHOLOGY 



of the pulmonary tissue would gradually press the air out of the affected 
area, while new air was not supplied by inspiration. Such a condition, 
however, must be rare. 

Pathological Anatomy. — The part affected by atelectasis is dark in 
color and is much reduced in size, so that when lobular areas are affected 
the pleural surface may be considerably depressed (see Fig. 237) . On sec- 
tion, the surface is smooth and generally dry, though in some instances 
passive hyperemia, which is generally present to some extent, reaches 
such a grade that bloody liquid flows freely from the surface of section. 
The term splenization is properly applied to such cases, whereas the in- 
stances in which the surface is dry are often spoken of as carnification. 
The lung does not crepitate, and sinks when placed in water. In the 
earlier stages the diseased portion may be inflated through the bronchial 
tubes; but when the condition has persisted, connective tissue over- 
growth springing from the septa causes permanent induration and 
collapse. The lung in such cases is hard and of a dark color, due to 
the deposit of hematogenous pigment, the result of disintegration 
of the blood present. The bronchi may be compressed, but sometimes 
atelectatic bronchiectasis results from the increased pressure of air sus- 
tained by the bronchi in consequence of the collapsed state of the 
lung tissue. 

INFLAMMATION, OR PNEUMONIA 

Classification. — Inflammation of the lungs, pneumonia, or pneu- 
monitis may arise in a variety of ways, and present itself in a number 
of widely varying forms, both as to the distribution and the nature of 
the pathological changes in the pulmonary structure. In all cases some 
irritant is conveyed to the lung either (a) from the upper air-passages 
or external world through the bronchi (bronchogenic pneumonia); (b) 
from some other part of the body through the blood (hematogenic 
pneumonia) ; or (c) from the pleura by direct extension or through the 
lymph-channels (pleurogenic pneumonia). 

Anatomically, pneumonia is classified according to the nature of the 
inflammatory products, and there are thus distinguished: fibrinous 
pneumonia, in which the air-vesicles and terminal bronchioles contain 
an exudate especially rich in fibrin; catarrhal, or bronchopneumonia, 
in which the exudate is composed of an albuminous liquid containing 
numerous epithelial cells and blood-corpuscles; purulent pneumonia, 
in which pus-cells are the noteworthy element in the exudate; cheesy 
pneumonia, in which cellular desquamation and cheesy necrosis are 
prominent; and productive or fibrous pneumonia, in which there is 
overgrowth of fibrous connective tissue. It is to be remembered, how- 
ever, that mixed cases are of frequent occurrence and that the essen- 
tials of inflammation are present in all types. Thus, in many in- 
stances localized areas of decided fibrinous pneumonia are found in the 
midst of larger areas of catarrhal pneumonia; some distinctly purulent 
exudation may be met with in many instances of fibrinous or catarrhal 
pneumonia; and more or less productive inflammation and fibrous 



DISEASES OF THE RESPIRATORY SYSTEM 



549 



overgrowth may be seen in any of the other varieties. Typical cases, 
however, present little mixture of the lesions. 

The terms "parenchymatous" and "interstitial pneumonia" are 
sometimes employed, but are of doubtful significance. The proper 
parenchyma of the lungs, the alveolar septa and their contained blood- 
vessels, are never the sole seat of inflammation, and the term "parenchy- 
matous pneumonia," as usually applied to inflammations of the lining 
epithelium of the air-vesicles, is, therefore, misused. It is appropriate 
to call the fibrous variety "interstitial pneumonia." 

Fibrinous Pneumonia 

Definition. — Fibrinous, or croupous, or lobar pneumonia is an acute 
infectious form of pneumonia, generally caused by the Diplococcits 
pneumonia, and usually involving an entire lobe or more than one lobe 
of one or both lungs. Pathologically, it is characterized by an exuda- 
tion within the air-vesicles and terminal bronchioles, mainly composed 
of fibrin; clinically the disease is marked by a definite and character- 
istic course. 

Etiology. — The important factor in the causation of fibrinous 
pneumonia is the Diplococcus pneumonia (Frankel-Weichselbaum). 
This micro-organism is found in the sputa and in the lungs, and is un- 
doubtedly the cause of the pneumonia in the great majority of cases, 
but some other micro-organisms seem able to occasion typical fibrinous 
pneumonia. Among these are the pneumobacillus of Friedlander, 
streptococci, staphylococci, the bacillus of typhoid fever, the bacillus of 
influenza, and the Bacillus coli communis. In some cases in which 
bacteria other than the diplococcus are supposed to be the cause there 
is, doubtless, mixed infection ; but it must be accepted at the present time 
that a number of micro-organisms are capable of causing the disease. 
The fibrinous pneumonia which occurs in the course of tuberculosis is 
certainly due to secondary infection, and the same thing frequently 
happens in the course of typhoid fever and influenza, though the specific 
bacilli of these diseases may alone cause pneumonia. 

The micro-organisms usually gain access to the lungs through the 
bronchi. In the case of the Diplococcus pneumonia the frequent oc- 
currence of this organism in the mouth and upper respiratory passages 
furnishes a ready explanation of one source of infection. More rarely 
the bacteria may be directly inspired from without, or, exceptionally, 
they may reach the lungs through the circulation. 

There are certain predisposing factors which have long been recog- 
nized clinically as causes of pneumonia. These probably act by render- 
ing the pulmonary tissues less resisting, or by increasing the virulence 
of the diplococci of the mouth. Among these causes are exposure to cold, 
injury of the lungs by traumatism, fatigue, and systemic depression. 

(For the description of the Diplococcus, see p. 280.) 

Latest studies have placed this disease, at least when caused by the 
pneumococcus, among the acute specific infections. There is almost 



550 



A TEXT-BOOK OF PATHOLOGY 



always a bacteremia. While admitting the effect of disposing causes in 
the production of the disease, attention has been called to acute localized 
congestions in the lung or bronchioles, as starting-points of the general 
involvement. Such, says Cole, are the most likely beginnings of the 
pneumonia because they offer colonizing places for pneumococci. 
The virulence of the bacterium has little relation to its pathogenicity, 
but the more virulent, the more fatal. There is no parallel between the 
severity of the infection and the extent of the anatomical lesions. The 
leukocytes and their phagocytic power are both increased toward the 
end of an attack. At its height the infection continues by reason of a 
state of balance between the phagocytic power of the leukocytes and 
certain antibodies in the blood on the one hand, and the infectious 
organisms on the other. When the defensive group neutralizes the 
offensive, the balance is destroyed and crisis takes place. (See Immun- 
ity and Pneumococcus, pages 256 and 280.) 

Pathological Anatomy. — The lesions most frequently involve the 
lower lobe of the right lung; next in order is the lower lobe of the left 
lung; the apices alone are least frequently involved. In all cases there 
is a tendency to the involvement of a whole lobe, and, as a rule, the 
entire area of disease is affected uniformly and simultaneously. There 
are wide variations, however; for, on the one hand, typical fibrinous 
pneumonia may occasionally appear as a more or less lobular disease 
(particularly in influenza), and, on the other hand, the process may 
spread from one part of the lung to another (pneumonia migrans). In 
typical cases not only is the process uniformly distributed, but it 
passes through distinct stages: first, of congestion, then of consolida- 
tion, and finally, of resolution. 

Stage of Congestion or Engorgement. — The affected area is dark-red 
m color; it is swollen and heavy, and on pressure crepitates less than a 
healthy lung. The pleura over the diseased part is dull and lusterless. 
On section through the lung, bloody liquid exudes, and when the part is 
compressed with the fingers this liquid shows a few air-bubbles. The 
condition is simply one of intense congestion, with exudation into the 
alveoli and terminal bronchioles of serous liquid and blood-corpuscles 
(see Fig. 232). Microscopically, the small blood-vessels of the septa are 
seen to be greatly distended and project inward toward the alveoli. 
Within the latter may be found many red corpuscles, a lesser number of 
leukocytes, and some detached epithelial cells. 

Stage of Consolidation, or Hepatization. — The diseased lung is now 
completely solid and liver-like in 'consistency (hepatization). It is 
swollen, and marked on the surface by indentations of the ribs. The 
surface of section is at first red in color (red hepatization, Plate 8), 
but later becomes white or gray, or in elderly persons (in whom the lungs 
are usually darkly pigmented from inhalation of dust) of a variegated 
appearance, resembling granite (gray hepatization, Plate 9). The cut 
surface is entirely dry, and is finely granular on account of the projection 
of small plugs of fibrin from the alveoli and bronchioles. The pleura 
is generally covered with fibrinous exudation. Microscopically, the 



PLATE 8 




Croupous pneumonia, stage of red hepatization (Bollinger). 



PLATE o 




Croupous pneumonia, stage of gray hepatization (Bollinger). 



DISEASES OF THE RESPIRATORY SYSTEM 



551 



alveoli are found distended with a network or particles of fibrin, in 
which the same cellular constituents as occur in the stage of congestion 
are embedded. The fibrinous network is beautifully demonstrated 
by staining the sections after the 
method of Weigert (Fig. 238). The 
blood-vessels are less prominent than 
in the first stage. As the disease ad- 
vances to the period of gray hepatiza- 
tion the number of leukocytes within 
the exudate increases and the blood- 
vessels become still less prominent 
(Figs. 239 and 240). This change of 
appearance is due to destruction of 
red blood-cells and leukocytes, a solu- 
tion of fibrin by enzymes from leuko- 
cytes, and the arrival of new leuko- 
cytes, which act as scavengers of the 
destroyed material. Under the mi- 
croscope the exudate has retracted 
from the septa and tiquefactive ne- 
crosis appears. 

Stage of Resolution. — Gradually softening of the exudate occurs and 
the lung becomes more moist. Puriform liquid may be squeezed from 
the surface of section, or may be seen in the bronchioles and bronchi. 
Crepitation is re-established. Microscopically, fatty degeneration of 




Fig. 238. — Red hepatization of the 
lung (from a photograph bv Dr. Wm. 
M. Gray). 




Fig. 239. — Croupous pneumonia: beginning gray 
hepatization (Karg and Schmorl). 



Fig. 240. — Advanced gray hepatiza- 
tion (from a photograph by Dr. Wm. 
M. Gray). 



the cells of the exudate is apparent. Softening is further contributed 
to by simple liquefaction. The result of these processes is emulsification 
of the exudate, which is finally carried off by the lymphatics or ex- 
pectorated. 



552 



A TEXT-BOOK OF PATHOLOGY 



Resolution occurs by action of the ferments liberated from the 
infiltrated cells upon their disintegration, and somewhat from the fer- 
ments of the bacteria. The digestion products of the ferment action 
are absorbed, not the cells and fibrin as such. 

Before the process of resolution is completed the epithelial cells 
of the alveoli and bronchioles proliferate, so as to repair the diseased 
portions. At the same time proliferative changes may be seen in the 
tissues of the septa. These conditions exist throughout the disease to a 
slight extent, but become more apparent in the stage of resolution. 
Eventually the lung is restored to its previous condition. 

Unusual Characters. — In some cases the pathological changes 
vary somewhat from the typical form described. Not rarely there are 
considerable congestion and even edema of the lung throughout the 
disease; in drunkards or cachectic individuals the exudate is more mark- 
edly hemorrhagic than is usually the case; and sometimes, particularly 
in instances accompanied by streptococcus infection, the exudate is more 
cellular than customary. In still other cases proliferative changes in 
the septa are prominent. 

In thinking of the outcome of a pneumonia one must not forget that, 
in this acute lobar form at least, large parts of the respiratory tissue are 
functionless, and are deprived of blood-, lymph-, and probably nerve- 
supply. 

Associated Lesions and Pathological Physiology. — The portions 
of the lung not involved by the pneumonic process are usually some- 
what emphysematous and congested, and edema may develop. The 
latter is, however, not so common as has often been assumed. The 
larger bronchial tubes, as a rule, remain normal or, at most, become 
congested. The finer bronchi are more frequently hyperemic, and 
excess of mucus coats the surface. In practically every case there is a 
certain degree of fibrinous pleurisy, either on the costal surface of the 
pleura or between the lobes. Extensive pleurisy is rare and serous 
exudation is uncommon. The pleurisy is directly attributable to the 
micro-organism which has caused the underlying pneumonia. 

Though fibrinous pneumonia is sometimes a local infection anatomic- 
ally, systemic intoxication is usually present, and general infection may 
further aid to develop widespread pathological changes. Leukocytosis is 
present in the great majority of cases; its absence is generally significant 
of unusually intense systemic intoxication. In fatal cases white clots 
are often detected in the chambers of the heart and in the large blood- 
vessels leaving the heart. Cardiac and respiratory embarrassment, 
often ascribed to mechanical causes, such as heart-clot or extensive 
consolidation, is probably in many cases due to the action upon the 
nervous system of the toxins of the disease. Myocardial degenerations 
aid in producing circulatory weakness. The heart muscle and the 
kidneys may suffer parenchymatous degeneration as in other febrile 
infections, and acute exudative inflammation (myocarditis, nephritis) 
may occur in either of these organs. Albuminuria is not infrequent, and 
albumoees may be found in the urine, especially during the stage of 



DISEASES OF THE RESPIRATORY SYSTEM 



553 



resolution. Calcium, chlorin, and sodium are decreased in excretion, 
while magnesium and potassium are increased. The spleen is enlarged 
and soft. 

Pericarditis is frequent, and endocarditis, either of the simple or of 
the malignant type, is more common than in any other acute infection, 
excepting rheumatism. Meningitis is occasionally noted. 

Fibrinous or pseudomembranous bronchitis, laryngitis, gastritis, 
colitis, and cystitis are sometimes met with. Inflammation of the joints 
and abscesses in various organs may occur. 

Unusual Terminations. — Secondary infection with pyogenic micro- 
organisms may lead to termination in abscess; or this result may be due 
to the fact that the pneumonia was primarily caused by active pus 
formers. The affected area may suffer gangrene even more com- 
monly than suppuration. Gangrene is especially prone to occur when 




Fig. 241. — Induration of the lung (carnification) in a case of pneumonia of five weeks' 
duration: a, a, a, New connective tissue of the septa; b, intra-alveolar proliferation of con- 
nective tissue; c, c, c, desquamated epithelium in the alveoli; e, e, e, new blood-vessels; 
/, lining epithelium of the alveoli (Kaufmann). 

the exudation is distinctly hemorrhagic and in cases in which the circu- 
lation is specially weak. Finally, resolution may be delayed and pro- 
ductive changes may occur in the septa and even within the alveoli. 
There results a solidification (carnification) of the lungs, or, as it is 
termed, fibrous pneumonia (Fig. 241). 

Catarrhal Bronchopneumonia 

Definition. — Catarrhal bronchopneumonia, or lobular pneumonia, 
is an acute inflammatory affection of the pulmonary tissue, occurring 
in localized areas and consequent upon inflammation of the terminal 
bronchioles. Pathologically, the disease is characterized by inflam- 
mation of the terminal bronchioles and by exudation into the alveoli 
of albuminous liquid containing desquamated epithelial cells, together 
with red blood-corpuscles and leukocytes in varying number; clinically, 
the disease is marked by an indefinite and irregular course. 

Etiology. — Catarrhal pneumonia may be produced experimentally 
in animals by causing them to inhale steam or various irritating vapors. 



554 



A TEXT-BOOK OF PATHOLOGY 



Still more characteristic lesions are produced when the vapors inhaled 
hold decomposing organic matter in suspension. The same result 
is accomplished by cutting the vagus nerves, as a consequence of which 
the vocal bands and esophagus are paralyzed and irritating secretions 
and particles of food are conveyed into the lung by inspiration. In 
man, tumors, enlargements of the thyroid gland, or inflammatory exuda- 
tion may compress the vagi and lead to forms of pneumonia similar 
to the experimental pneumonia of dogs. Somewhat analogously, 
in the late stages of various diseases, particles of food and mucous secre- 
tions may sink to the dependent parts of the lungs, or may be drawn in 
by the inspiratory air and set up catarrhal pneumonia in the parts al- 
ready predisposed to inflammation by hypostatic congestion {hypostatic 
pneumonia) . Of the same etiological sort are the catarrhal pneumonias 
which occur in diphtheria, epithelioma of the larynx, and inflammatory 
conditions of the mouth and pharynx, in which irritating particles are 
carried to the finer bronchi by inspiration (aspiration pneumonia, 
deglutition pneumonia) . Catarrhal pneumonia of this kind is not infre- 
quent in the newborn as a result of vigorous inspiratory efforts made 
while the head is descending through the vagina. 

Most frequent, however, of all forms of catarrhal bronchopneumonia 
is that which occurs in the course of measles, whooping-cough, influenza, 
or other infectious fevers attended with bronchitis. The manner of in- 
volvement of the alveolar structures will presently be described ; for the 
present it may be said that the inflammatory process extends from the 
bronchi by continuity and contiguity, or by aspiration of irritating 
bronchial secretions. 

The immediate cause of catarrhal pneumonia is some bacterium, 
the most frequent being the Diplococcus pneumonia*, which occurs 
in over 50 per cent, of all cases, either alone or in combination 
with the Streptococcus pyogenes, staphylococci, the pneumobacillus 
of Friedlander, the bacillus of influenza or of typhoid fever, or the 
Bacillus coli communis. Any of the other forms named, and especi- 
ally the pyogenic micrococci, may cause catarrhal pneumonia without 
the diplococcus of Friinkel; but in the case of fevers (typhoid fever, 
influenza) in which the specific micro-organisms are found there is 
usually mixed infection with the Diplococcus pneumoniae. 

Pathological Anatomy. — The lesions vary somewhat in different 
cases, and we may distinguish three important types: the simple, or 
ordinary catarrhal bronchopneumonia, the hypostatic form, and 
aspiration pneumonia. 

1. Simple Catarrhal Bronchopneumonia. — The lung in such cases 
presents more or less distinct external appearances. On the pleural 
surface may be seen lobular areas of dark- or light-red or grayish color, 
which are somewhat elevated and harder than the normal lung. Sur- 
rounding these the pulmonary tissue is emphysematous, while here and 
there may be seen dark-red or lead-colored and somewhat depressed 
areas of pulmonary collapse (atelectasis). The lung as a whole is crepit- 
ant, while the pneumonic and atelectatic areas are consolidated and air- 



DISEASES OF THE RESPIRATORY SYSTEM 



555 



less and sink in water. On section through the lungs the same general 
appearances are visible, though the consolidated patches are most 
abundant near the surface. Both lungs are, as a rule, involved, and any 
portion is liable to the disease. The smaller and medium-sized bronchi 
and the bronchioles contain mucopurulent secretion, which may be 
squeezed out; the areas of pneumonic consolidation are smooth and 
moist on the surface of section, or exceptionally somewhat granular 
as a result of admixture of some fibrinous exudate. Occasionally there 
may be puriform liquid or small purulent collections around the bron- 
chiole in the center of the lobule. The area of collapse (atelectasis) is 
dark red, as a rule, and on pressure bloody liquid exudes. 

In the very earliest stages of the disease the areas of consolidation 
and collapse may be inflated by inserting a tube into the bronchus 
supplying the part and by blowing gently into it. Later this is not pos- 
sible, as the consolidation increases. At the same time it is noted that the 



consolidated areas become lighter in color, until at last they are grayish 
yellow; while the areas of collapse become pneumonic and present a 
similar change of color. 

Microscopically, the terminal bronchioles and alveolar passages 
present somewhat swollen walls and contain variable amounts of fluid 
exudate with many desquamated cells. In the areas of consolidation 
the alveoli and the air-sacs are filled with liquid and variable numbers of 
epithelial cells, red corpuscles, and leukocytes (Fig. 242). The epi- 
thelial cells are desquamated from the lining membrane either singly 
or in groups, and there is evidence that active proliferation is taking- 
place as well. In most cases the number of red corpuscles and leuko- 
cytes is small, but in some instances, particularly in cases in which 
streptococci and staphylococci are operative, the exudation may be 
quite hemorrhagic or, later, purulent. The alveolar septa regularly pre- 
sent considerable round-cell infiltration, and the blood-vessels are sur- 



Fig. 242. — Catarrhal pneumonia (Karg and Schmorl). 




556 



A TEXT-BOOK OF PATHOLOGY 



rounded by emigrated leukocytes. The blood-vessels in the septa are 
distended and tortuous. 

The atelectatic areas present even greater congestion of the blood- 
vessels, and the alveolar cavities are obliterated by the collapse of the 
walls, or contain, at most, a little hemorrhagic exudate. The epithelial 
cells tend to lose their characteristic shape and become cuboidal. 

As resolution advances, the cellular exudate becomes lighter in color 
as a result of fatty degeneration, and eventually it is absorbed or ex- 
pectorated. Coincidently the round-cell infiltration disappears from the 
septa, and the pulmonary tissue returns to the normal, excepting that 
the epithelial cells of the alveoli tend to remain more or less cuboidal 
for a time. Resolution probably takes place as in the case of fibrinous 
pneumonia. 

Pathogenesis. — The manner of development of the lesions is of con- 
siderable interest. In the ordinary catarrhal bronchopneumonia now 
under discussion there is always a primary bronchitis of the terminal 
bronchioles, a bronchiolitis, or capillary bronchitis, as it is termed. This 
may be spread to the alveolar structure in several ways. In most in- 
stances, no doubt, the inflammation travels downward along the bron- 
chioles to their termination by continuity, or outward through their 
walls to the surrounding alveoli by contiguity. In either .case there 
results a patch of catarrhal pneumonia surrounding a terminal bron- 
chiole. Less commonly the affected lobule first becomes atelectatic and 
then pneumonic. The atelectasis results from the obstruction of the 
bronchioles by mucus or by their swollen walls, and is due to the gradual 
absorption of the air contained within the alveoli and the inability of 
more to enter (see Atelectasis). Subsequently the collapsed area 
becomes inflamed by the entrance of micro-organisms from the bron- 
chioles or by extension of surrounding inflammation. 

Unusual Characters. — Marked variations are seen in the nature of 
the process and in its distribution. In some instances there is but little 
pneumonic consolidation, while the bronchiolitis, or capillary bronchitis, 
is a striking feature. In other cases the exudate is decidedly hemor- 
rhagic or purulent, and it may in certain areas be quite fibrinous. 
Regarding the distribution, the most striking variation is the tendency 
in some cases to lobar involvement by confluence of the lobular areas 
(pseudolobar form) . 

Associated Lesions. — The constant association of "bronchitis has been 
sufficiently noted. Pleurisy is less common than in fibrinous pneu- 
monia, but the patches near the surface are frequently covered with 
fresh pleural exudation. It has long been recognized that purulent 
pleurisy is more apt to occur after pneumonia in children than in adults, 
and in many of these cases the antecedent pneumonia is catarrhal. Wide- 
spread toxic and infective lesions may occur, as in fibrinous pneumonia. 

Unusual Terminations. — In cases in which micro-organisms, more 
virulent than usual, cause the pneumonia, suppuration and gangrene 
may result. Fetid and pultaceous foci, or purulent collections sur- 
rounded by considerable areas of congestion and inflammatory edema, 



DISEASES OF THE RESPIRATORY SYSTEM 



557 



result. In other instances the process of resolution is slow, and fibroid 
overgrowth of the septa and proliferation of connective tissue within the 
alveoli ensue, with the production of more or less extensive sclerotic- 
hardening and contraction of the lung structure. Within such areas 
the alveolar exudate may lie for a long time as a fatty mass; but this is 
very unusual; and true caseation, of which so much was formerly said, 
does not occur. The instances in which this was supposed to have 
occurred were cases of subsequent infection with tubercle bacilli, or 
cases of tuberculous pneumonia ab initio. 

2. Hypostatic Pneumonia. — The bases and posterior portions of the 
lungs are commonly involved in these cases. The process occurs as a 
terminal affection in many diseases. It begins as an intense hypostatic 
congestion and hemorrhagic edema of the dependent parts of the lungs. 
Subsequently, the irritants which make their way to the congested area 
through the bronchi set up a form of inflammation of the terminal 
bronchioles and air-vesicles which is largely catarrhal, but more fibrinous 
than ordinary bronchopneumonia. The inflammatory process is also 
more diffuse, and is at the most insignificant compared with the ante- 
cedent and associated congestion and edema. 

3. Aspiration Pneumonia. — Of the dust which we constantly inhale, 
the greatest part is arrested in the upper air-passages or in the larger 
bronchi, and is expectorated. A part, however, reaches the finer bronchi 
and bronchioles, and sets up a certain amount of local irritation and 
congestion, with desquamation of epithelial cells and emigration of 
leukocytes. Ordinarily, these processes are exceedingly trivial and can 
rarely be demonstrated. In persons, however, whose occupations 
(e. g., steel-grinding, coal-mining, marble-cutting, etc.) subject them to 
excessive dust inhalation the pulmonary changes are extensive and 
severe. This is one form of aspiration bronchopneumonia, but the irri- 
tation rarely stops at the point of catarrhal inflammation; on the con- 
trary, the irritant particles penetrate the walls of the bronchioles and 
are distributed by the lymphatics, causing fibroid changes of greater or 
less extent. The pneumonia thus produced is, therefore, more appro- 
priately considered as a form of fibrous pneumonia (q. v.). 

In the course of various affections of the pharynx, larynx, trachea, 
and bronchi during anesthesia, as well as in cases in which through palsy 
of the larynx, or through general depression, particles of food or secre- 
tions of the mouth enter the air-passages, irritating matters may be in- 
spired or "aspirated" into the finer divisions of the bronchial system. 
There results intense local irritation, with catarrhal inflammation and 
consolidation. The exudate is largely epithelial, but more often serous, 
hemorrhagic, or purulent than in simple catarrhal pneumonia. The 
condition may be circumscribed to small patches, but if large particles 
are aspirated and the larger bronchial tubes are obstructed, widespread 
consolidation, of the character described, results. The inflammatory 
process in these cases of aspiration pneumonia are habitually intense, 
and often terminate in suppuration or necrosis, with considerable sur- 
rounding hyperemia and edema. 



558 



A TEXT-BOOK OF PATHOLOGY 



Cheesy or Tuberculous Pneumonia 

Definition. — Cheesy or tuberculous pneumonia is an acute or sub- 
acute form of pneumonia caused by the tubercle bacillus, involving 
lobular areas or, by confluence of such, an entire lobe or lung. Patho- 
logically, it is characterized by proliferation and desquamation of epi- 
thelial cells, infiltration of the alveolar septa, and, finally, by cheesy 
necrosis in the area of disease. Clinically, the disease presents itself 
as a more or less acute pneumonic tuberculosis. Caseous pneumonia is 
frequently associated with miliary or peribronchial tubercles, affecting 
the alveoli adjacent to the tubercles. 

The pneumonic form of phthisis florida is a caseous pneumonia. 
Bronchopneumonia of coccus origin may supervene upon chronic ulcera- 
tive phthisis, or tuberculous lesions may be implanted upon a pneumonia. 

Etiology. — Cheesy pneumonia as an independent condition is 
more common in children than in adults. The immediate cause is the 
tubercle bacillus. Infection occurs by rupture of a tuberculous gland 
or cavity into one of the bronchi and dissemination of the infective 
material throughout the lung. Likewise, bacilli may be inhaled from 
outside, or from tuberculous foci in the bronchi, larynx, or nose. In 
cases of disseminated tuberculosis of the lungs areas of caseous pneu- 
monia are habitually encountered in the pulmonary structure between 
the tubercles. Finally, infection may take place through the blood, 
but the occurrence of caseous pneumonia rather than miliary tubercu- 
losis in such cases is assuredly rare. Theoretically, it is possible to 
have a sudden and overwhelming generalization of the tubercle bacil- 
lus with involvement of a ichole lung, but such an occurrence is rare. 
Such cases have been described, but it is difficult to estimate the 
importance of the tubercle bacillus in the presence of other germs 
capable of producing the inflammation. The process is a catarrhal 
pneumonitis universalis without the tubercular changes characteristic 
of caseous pneumonia. 

It has, indeed, been questioned whether the tubercle bacillus alone 
can cause this caseous pneumonia, since the typical tuberculous in- 
flammation is a productive one of lymphatic or interstitial origin. On 
the other hand, a caseous pneumonitis without tubercle bacilli is not 
known. In those cases reported as primary diffuse tuberculous pneu- 
monia the pre-existence of a focus discharging bacilli into the trachea 
or bronchi could not be satisfactorily excluded. 

Mixed infection with Diplococcus pneumonia' is not infrequent, but 
it is not, as some investigators have maintained, essential to the disease. 

Pathological Anatomy. — In its most typical form caseous pneu- 
monia is a lobular process beginning around the terminal ends of the 
bronchioles, where the infective material lodges. The lung presents on 
section areas of consolidation not unlike those seen in catarrhal broncho- 
pneumonia. At first these are congested and red in color, but very soon 
degenerative changes cause a grayish or yellowish color. The surface 
of section is usually smooth, but often somewhat granular from asso- 



PLATE to 




Subacute caseous (tuberculous) pneumonia (Bollinger). 



DISEASES OF THE RESPIRATORY SYSTEM 



559 



ciated fibrinous exudation. When abundant infection has occurred the 
areas may be thickly set, and a lobar form is thus established (Plate 10) ; 
or there may be a gradual involvement of new areas, receiving their 
infection from those first formed, causing a similar, but less uniform, 
lobar pneumonia. 

The distribution of caseous bronchopneumonia depends upon its 
origin. If this be from the upper air-passages, the involvement may be 
more or less regular and symmetrical, while if entrance of the bacilli 
be gained through a rupture of a gland into a bronchus, it will follow the 
course of this tube and spread from it. 




Fig. 243. — Peribronchial tubercle of the lung and caseous pneumonia of the adjacent 

alveoli. 

Caseous pneumonia shows no tendency to resolution, but, on the 
contrary, tends to progressive cheesy degeneration, and at last to the 
formation of cavities. The entire lung may be riddled with small ex- 
cavations, presenting ragged, cheesy walls. Usually the cavities are 
small, even though there be few; exceptionally, large ones are seen. 
Though resolution does not occur, limited areas may be healed by 
reactive fibrous overgrowth springing from the alveolar septa and en- 
capsulating the diseased area, or penetrating it, and transforming the 
whole into a fibrous mass. 

Microscopically, the exudation has many of the characters seen in 
catarrhal bronchopneumonia. Essentially, the exudate is cellular, 
and is principally composed of large epithelial cells. These are the des- 
quamated and proliferated lining cells of the alveoli. A smaller number 



560 



A TEXT-BOOK OF PATHOLOGY 



of red blood-corpuscles and leukocytes is noted, but they are unessential. 
Sometimes a fibrinous network may be seen in the alveoli, but quite as 
often this is wholly wanting. The blood-vessels are engorged at first, 
and the septa are infiltrated with round and spindle cells. The walls 
of the blood-vessels themselves may be thickened by proliferation of 
the connective tissue. As the process advances the cellular exudate 
and the alveolar walls as well undergo cheesy degeneration, and pre- 
sent a granular appearance under the microscope (Fig. 243). 

Associated Lesions. — Cases of typical caseous pneumonia, as above 
described, are rare; as a rule, more specific tubercular lesions (tubercles) 
are associated. The smaller bronchi are commonly attacked in asso- 
ciation with caseous pneumonia, and tuberculous bronchitis and peri- 
bronchitis tending to cheesy change result. The pleura may be cov- 
ered with inflammatory exudation, or may present miliary tubercles over 
the area of disease. Associated pleural involvement is especially com- 
mon between the lobes. The lymphatic glands of the anterior medias- 
tinum and around the bronchi are frequently enlarged, and may be 
cheesy in the later stages. 

Fibrous Pneumonia 

Definition. — Fibrous, or productive, pneumonia is a chronic process 
resulting from continued irritation, and involving small or large areas 
of the pulmonary structure. Pathologically, it is characterized by over- 
growth of connective tissue, and clinically it is marked by signs of more 
or less extensive mechanical impairment of the pulmonary functions. 

Classification. — Several quite distinct forms, depending upon differ- 
ent modes of causation, may be described. The principal varieties are: 
(1) The pneumonokonioses, or fibrous pneumonias, due to dust inhala- 
tion; (2) the secondary indurative pneumonias, such as sometimes follow 
croupous, catarrhal, or caseous pneumonia, or more frequently chronic 
congestion of the lungs or atelectasis; (3) pleurogenetic fibrous pneu- 
monia, in which the process arises by extension of chronic pleural dis- 
ease ; and (4) peribronchial and perivascular fibrous pneumonia, in which 
the process follows the bronchi and pulmonary arteries. 

1. Pneumonokoniosis. — Of the dust we constantly inhale, but a 
small part reaches the finer divisions of the bronchial tree. Most of it 
adheres to the walls of the upper respiratory tract and is discharged with 
the sputa, either free or enclosed in leukocytes or epithelial cells {dust- 
cells, Staubzellen). When fine particles reach the terminal bronchioles 
they occasion catarrhal inflammation, marked by proliferation of the 
epithelium and exudation of leukocytes. These cells may envelop the 
irritant particles and remove them through the expectoration. When, 
however, the dust has sharp edges (as in coal-dust, iron-dust, marble- 
dust, etc.), and especially when the quantity inhaled is considerable, 
removal by expectoration becomes more difficult. In such cases the 
foreign particles penetrate the walls of the bronchioles and alveoli, 
passing between the epithelial cells. They may be arrested in the 



DISEASES OF THE RESPIRATORY SYSTEM 



561 



alveolar septa and in the tissue surrounding the bronchioles by the for- 
mation of a zone of inflammatory exudation, which eventually organizes, 
forming a fibrous capsule. Some of the particles, however, move along 
the lymph-spaces into the lymphatic vessels, being carried by phagocytes 
or floating free in the liquid. These particles may be arrested at various 
points along the lymphatics, and may occasion fibrous thickening of the 
vessels or of the perilymphatic tissue. The greater portion, however, 
passes to the lymphatic glands at the root of the lung and surrounding 
the bronchi, and indurative enlargement of these structures results. In 
exceptional instances the irritant particles may be conveyed still further, 
being deposited in the glands about the smaller curvature of the stomach 
and beneath the fissure of the liver. This unusual distribution in a direc- 
tion opposite the usual lymphatic current is explained by the assumption 
that obstruction of the larger pulmonary lymphatics causes a reversal 
of the current. Metastatic distribution of dust-particles may also be 
due to rupture of one of the affected lymphatic glands into a vein. 
(See discussion of Pneumonokoniosis, page 99.) 

Pathological Anatomy. — The appearance of the lung varies with 
the amount of dust inhaled and with its nature. In cases of moderate 
degree small areas of fibrous thickening, with puckering, are the only 
abnormality. On section, these are found to be hard and of grayish 
color; often, however, darkly pigmented, owing to the character of the 
particles inhaled as well as on account of the formation of hemorrhagic 
pigmentation. The fibrous tissue may be arranged in a stellate fashion, 
or concentrically around a nucleus of foreign matter. Secondary changes 
are not uncommon; calcification is frequently observed, and true bone- 
formation is occasionally noted. Such areas of localized pneumono- 
koniosis are very commonly met with near the apices. 

More extensive induration is rare, and is rather more frequent 
at the bases. Large areas of induration may completely destroy the 
vesicular character of the lung structure. Firm bands of connective 
tissue may follow the bronchi and radiate into the peripheral portions 
of the lung, or thickened trabecular may pass from the pleural surface 
toward the interior, or, again, a more uniform sclerosis may exist 
throughout the organ. The organ is contracted; the pleura, as a rule, 
is thickened and drawn inward; and the bronchi may be widely dilated 
as a result of the traction of the contracting connective tissue and as a 
consequence of accumulating secretions within. Extensive adhesions 
to the chest wall often cause deformities of the chest, and the pericar- 
dium, heart, and other mediastinal structures may be drawn from their 
normal positions. 

In rare cases the epithelium of the alveoli and finer bronchioles 
proliferates, and later undergoes a certain amount of fatty degenera- 
tion, giving rise to an appearance not unlike caseation. In still other 
cases necrosis, suppuration, and cavities (non-tuberculous) are observed. 

Microscopically. — In the beginning stages round-cell infiltration 
and connective-tissue proliferation may be seen around the foreign 
particles in the septa, and a certain amount of catarrhal inflammation 

36 



562 



A TEXT-BOOK OF PATHOLOGY 



may be present in the alveoli. Sharp-edged particles often occasion 
small hemorrhages. In the later stages dense sclerotic tissue charac- 
terizes the process. Proliferative inflammation of the epithelium of the 
alveoli may be present, but more often the cells undergo atrophy and 
disappear. 

Varieties. — Certain varieties, dependent upon the kind of dust 
inhaled, have been described. The term anthracosis is applied to those 
instances in which coal-dust is the irritant. To a moderate extent this 
is seen at every autopsy in persons of adult age, but the cases in which 
conspicuous sclerosis has occurred from this cause are met with only in 
coal-miners and persons of similar occupations. The lung is of a marble- 
like or slate-like appearance, and the lymphatic glands around the 
bronchi are intensely pigmented. Siderosis is the designation of the 
cases of pneumonokoniosis due to iron-dust, as seen in grinders, founders, 

etc. Chalicosis is the term applied 
to the form due to stone-dust, as 
seen in potters, marble-cutters, etc. 

The variety of pigment may be 
distinguished by microchemical re- 
actions. 

2. Secondary fibrous pneumonia 

sometimes occurs after croupous or 
catarrhal pneumonia, or atelectasis, 
and in these cases appears in the 
form of uniform or localized indura- 
tion of the pulmonary structure. It 
is due to reactive inflammation of 
the septa, causing thickening of the 
latter, as well as proliferation within 
the alveolar exudate. Similar reac- 
tive fibrous change is seen in some 
cases of caseous pneumonia, and in 
'<■«— ^ chronic phthisis the cavities are quite 

Fig. 244. — Fibrous pneumonia secondary ,, , , , . 

to chronic pleurisy (Kaufmann). generally walled by fibrous tissue. 

Finally, chronic congestion of the 
lung, such as occurs in valvular diseases of the heart, particularly mitral 
disease, frequently leads to diffuse sclerosis of the lung. Such cases are 
distinguished by dilatation of the veins and by hematogenous pigmen- 
tation. 

3. Pleurogenic fibrous pneumonia is an occasional consequence 
of chronic pleurisy. The lung presents on section dense trabecular of 
fibrous tissue, which extend from the thickened and sclerotic pleura 
deep into the pulmonary structure (Fig. 244). 

4. Peribronchial and perivascular fibrous pneumonia may be asso- 
ciated with the pleurogenic form, or the overgrowth of connective tissue 
around the bronchi and vessels may start at the root of the lung and 
extend toward the periphery. The latter form has been described by 
some observers as especially liable to result from syphilis. More moder- 




DISEASES OF THE RESPIRATORY SYSTEM 



563 



ate peribronchial and perivascular fibrous pneumonia occurs in asso- 
ciation with other forms, as the pneumonokonioses and secondary 
fibrous pneumonias, but in these cases it is but a minor part of the 
process. 

Congenital Syphilitic Pneumonia. — A form of productive pneumonia, 
as distinguished from fibrous pneumonia in the strict sense that the latter 
is characterized by formation of sclerotic fibrous tissue, is met with in 
congenital syphilis. This is the pneumonia alba of some writers. Spiro- 
chete pallida' are present in countless numbers. It is characterized by 
great proliferation of round and irregular connective-tissue cells, with 
more or less multiplication and degeneration of epithelial cells in the 
alveoli and bronchioles. The lung is solid, airless, and white in color 
(white pneumonia). Gummata may be associated. 

Purulent Pneumonia 

Definition. — Purulent pneumonia is an acute form of pneumonia 
in which the exudate undergoes purulent softening, usually caused 
by the pus producing cocci. Pathologically, it is characterized by 
purulent and hemorrhagic exudation in the connective tissue, lymphatic 
channels, or terminal bronchioles and alveoli; and clinically it is marked 
by evidences of intense septic infection as well as by great pulmonary 
embarrassment. This subject is given a separate heading by reason 
of its clinical rather than pathological importance, as the dominant 
factor is septicemia. 

The infection in purulent pneumonia may reach the lungs through 
the bronchi (bronchogenic), the blood-vessels (hematogenic), or the sub- 
pleural lymphatics (pleurogenic or lymphogenic). 

Bronchogenic purulent pneumonia has already been referred to 
in the description of fibrinous pneumonia and catarrhal broncho- 
pneumonia. It is particularly frequent in the latter, in some cases of 
which considerable purulent exudation may be seen in the alveoli or, 
in the form of small purulent collections, in the intervesicular septa. 
The pathological changes are those of catarrhal pneumonia, with an 
excessive infiltrate of polynuclear leukocytes. These are instances of 
intense infection, and the majority of such cases are due to the Strepto- 
coccus pyogenes or to staphylococci. The pneumococcus may, how 7 ever, 
be found alone. The most decided purulent bronchopneumonia is seen in 
instances of aspiration pneumonia secondary to a suppurative process in 
the upper respiratory passages, in wdiich particles of infective material 
are inspired and lodge in the bronchioles. 

Purulent pneumonia is rarely met in the course of fibrinous pneu- 
monia, but sometimes occurs as a terminal condition. Abscesses of con- 
siderable size may be formed. 

Hematogenic purulent pneumonia is secondary to suppurative or 
gangrenous processes in other parts of the body, and is a manifestation 
of pyemic infection. It is frequent in puerperal septicemia, in suppura- 
tive osteomyelitis, and like conditions. The micro-organisms are 



564 



A TEXT-BOOK OF PATHOLOGY 



carried by the veins to the right heart, and may first set up malignant 
endocarditis, from which embolism takes place, or they may pass 
directly through the right heart to the lungs. As a rule, the micro- 
organisms in question are either streptococci or staphylococci; but in 
certain specific infections (as typhoid fever) the specific organisms may 
alone occasion purulent pneumonia. 

When large embolic masses reach the lungs occlusion of larger 
branches of the pulmonary artery occurs and hemorrhagic infarcts are 
formed. In the earliest stages these appear as more or less well-circum- 
scribed areas of hemorrhagic infiltration of dark-red color. Very soon 
change of color occurs, and the foci alter to a grayish, then a yellowish, 
color, and finally liquefy, forming suppurative cavities, with irregular 
walls. The lesion at this stage constitutes what clinicians describe as 
abscess of the lung, and though such abscesses may result from fibrinous 
pneumonia or other conditions, the most frequent variety is that follow- 
ing embolism or thrombosis of the pulmonary artery. The tissue 
around the abscess is intensely engorged and edematous, and not rarely 
quite hemorrhagic. Microscopically, the lesion in the earlier stages 
presents the appearances of a catarrhal and hemorrhagic pneumonia. 
The abscesses frequently break into the bronchi and discharge their 
contents; more rarely rupture into the pleural sacs occurs. The pleura 
itself is intensely inflamed over the embolic areas, and, as a rule, is 
covered with fibrinopurulent exudate. Extensive purulent pleurisy 
{empyema) may occur. 

When the micro-organisms reach the lung in a more disseminated 
manner they pass at once to the smaller arterioles and capillaries. 
The organisms circulating in the blood are, in all probability, single, 
but when they meet the intricacies of the pulmonary capillary network 
they are arrested. The oxygen present favors agglutination of bacteria, 
especially of the pneumococci. The swelling of the vascular endo- 
thelium by toxic agencies, in all general infections, favors the settling 
of bacteria. 

Embolic infarcts are wanting in such cases, but there is diffuse 
serous, hemorrhagic, catarrhal, and purulent exudation, which causes 
consolidation of a somewhat gelatinous character. Small foci of suppu- 
ration (miliary abscess) may be seen, and the purulent process may vis- 
ibly extend to neighboring parts of the lung along the lymphatic vessels. 

Terminations. — In either of the above forms, the localized embolic 
or the diffuse, necrosis or gangrene of the pulmonary tissue may occur. 
Occasionally recovery takes place by absorption of the purulent exu- 
date or by its discharge. As a rule, the disease is fatal. 

Pleurogenic purulent pneumonia follows intense pleurisy, usually 
of purulent type. Infection of the subpleural lymphatics first ensues, 
and later the purulent process extends into the lung within and around 
these vessels (purulent lymphangitis and perilymphangitis), in the form 
of yellowish streaks or bands, which surround the veins and bronchi 
and follow the interlobular fibrous tissue in various directions. The 
lobules of the lung may be so pushed apart that the term pneumonia 



DISEASES OF THE RESPIRATORY SYSTEM 



565 



deskcans is quite applicable. The proper substance of the lung adjoin- 
ing the paths of purulent invasion, and under the pleura, frequently 
shows the same form of hemorrhagic and purulent pneumonia as occurs 
in the diffuse hematogenic form. 

Associated Lesions. — Widespread pyemic and toxic lesions are 
often found in association with purulent pneumonia, but they are often 
merely coincident results of the same primary disease to which the 
pneumonia owed its origin, rather than the consequences of the purulent 
pneumonia itself. Secondary infections may, however, occur, such as 
malignant endocarditis of the left side of the heart, septic nephritis, 
and the like. 

GANGRENE 

Gangrene of the lung results from the action of putrefactive micro- 
organisms in necrotic areas of the lung tissue. It may be the conse- 
quence of direct extension of carious conditions of the ribs or other 
adjacent bony structures through the pleura into the lung, or of the 
extension of necrotic processes from ulcers or cancerous disease of the 
esophagus or stomach. In other cases the infective materials reach the 
lung through the inspired air, coming from ulcerative processes in the 
upper air-passages or from without. When foreign bodies lodge in the 
bronchi, or the latter are obstructed by the pressure of tumors or 
aneurysms, there may be, first, more or less congestion and pneumonic 
consolidation, followed by secondary infection and gangrene. In still 
other instances the infective material reaches the lung through the 
blood. Finally, gangrene is sometimes a terminal process in pneu- 
monia, tuberculosis, and hemorrhagic infarction of the lungs. Certain 
general conditions predispose more or less to it. Thus, in diabetic indi- 
viduals, congestions or pneumonia are prone to terminate in this way, 
and engorgement of the veins or passive hyperemia always renders the 
lung more liable. 

Pathological Anatomy. — Gangrene may appear as a circumscribed 
or diffuse process. In circumscribed gangrene more or less extensive areas 
of lung present a dark, reddish, brownish, or even greenish appearance, 
and are surrounded by a zone of intense congestion or of pneumonic 
consolidation, often of purulent or hemorrhagic type. The diseased 
part is soft, pultaceous, and foul in odor. Later it may break down into 
a putrid mass, and may discharge through the bronchial tubes, severe 
pulmonary hemorrhages sometimes occurring at the same time. The 
bronchi and the blood-vessels often escape the process, and may pass 
through the gangrenous area without being themselves materially 
affected; but usually the bronchi are penetrated, and the blood-vessels, 
after they become occluded by thrombosis, suffer the fate of the other 
tissues. The process may extend widely from a single focus, or react- 
ive inflammation may establish a fibrous capsule, and after discharge 
of the gangrenous material through the bronchi, healing by the forma- 
tion of a scar may terminate the disease. 

Diffuse gangrene does not differ much in its general appearances, 



566 



A TEXT-BOOK OF PATHOLOGY 



but is less intense and, in general, more widespread. The affected area 
is of a dark-red or greenish-black color, soft and edematous, or some- 
times dry, and has a somewhat fetid odor, as in the circumscribed form. 
Spots of hemorrhagic infiltration and of softening, with formation of 
cavities, may be noted. 

The sputa in gangrene are mucopurulent, of a yellowish-gray or 
brownish color, and intensely fetid. When placed in a conical vessel 
they separate into three layers: the upper frothy, the lower puriform 
and brownish in color, and the middle layer more fluid and yellowish. 

INFECTIOUS DISEASES 

Tuberculosis 

Tuberculosis of the lungs is usually a local process at first, but in 
many cases becomes generalized by subsequent spread of the infec- 
tion. Sometimes the pulmonary disease is from the beginning only a 
part of a general tuberculosis. 

Infection of the lungs occurs through the bronchial tubes (broncho- 
genie tuberculosis), through the blood-vessels (hematogenic tuberculosis), 
or through the lymphatic system (lymphogenic tuberculosis) . 

1. The first of these three modes of infection is probably far more 
frequent than the other two combined. The tubercle bacillus, dissemi- 
nated by the drying of sputa or other infected discharges from tubercu- 
lous patients, is carried directly to the lungs in the inspired air or, more 
rarely, it may lodge in the pharynx, upper air-passages, or bronchi, and 
produce primary tuberculous lesions from which the lungs are second- 
arily affected. Immediate infection of the lungs is more frequent than 
the secondary form. 

2. Hematogenic infection is clearly evident in cases in which a tu- 
berculous disease of some other part (as the bronchial glands, prostate, 
bones, etc.) has become generalized by entrance of the tubercle bacilli 
into the circulation and in which tuberculous lesions make their ap- 
pearance in various parts of the body, including the lungs. Sometimes 
the point of rupture of a tuberculous focus into a vein has been demon- 
strated. The bacilli entering the venous circulation are carried through 
the right heart to the lungs, and are, for the most part, arrested in 
them. When finely divided in the blood some may pass through the 
pulmonary circulation and may thus be distributed widely through the 
body. In many cases, however, the lungs arrest all the bacilli and be- 
come affected without general tuberculosis. Sometimes perhaps the 
lungs are infected through the vascular channels without pre-existing 
lesions elsewhere. This may occur when tubercle bacilli traverse the 
mucous membranes and enter the circulation without causing a primary 
lesion at the portal of entrance. How frequently this may happen 
cannot very well be estimated, but many facts speak in favor of its 
not infrequent occurrence. Tuberculosis of the mesenteric glands 
without intestinal lesions is not uncommon, and cannot be explained 



DISEASES OF THE RESPIRATORY SYSTEM 



567 



except on the assumption that the bacilli passed through the mucosa 
and into the lymphatics without causing a lesion at the portal of en- 
trance. Other facts (as, for example, the occurrence of primary tuber- 
culosis of bones) indicate that the bacilli may be distributed widely in 
the circulation without local lesions at the places where they entered 
the body. Lung tuberculosis can doubtless occur in the same way, 
and some authorities believe this a frequent mode of infection. In view 
of the demonstrated intercommunicability of human and bovine tubercu- 
losis, the possibility of pulmonary infection from the consumption of 
tuberculous meat and milk and the passage of the bacilli through the 
mucosa of the digestive tract is apparent. 

In some cases of hematogenic tuberculosis the bacilli gain entrance 
to the blood in an indirect manner, as, for example, when a lesion of the 
abdominal or thoracic lymph-glands penetrates the thoracic duct. The 
bacilli carried in the lymphatic stream pass through the thoracic duct 
and eventually reach the blood and are disseminated in the lungs and 
other organs. 

Localized hematogenic tuberculosis of the lungs may occur when an 
old tuberculous lesion of the lung or a caseous bronchial lymph-gland 
penetrates a branch of the pulmonary artery and thus disseminates 
bacilli in the lungs. This mode of occurrence of the disease in the lung is 
rarely observed. 

3. Lymphogenic infection of the lungs is secondary to tuberculous 
pleurisy, tuberculous bronchial lymphadenitis, mediastinitis, etc. 
In these cases the pleural and subpleural lymphatics become infected 
and the process spreads along these channels to the lungs. 

A combination of the aerogenie and lymphogenic routes is possible. 
It is believed that tubercle bacilli may settle on the mucosa of the upper 
air- and alimentary passages, be carried thence to the regional lymph- 
nodes, and finally to the mediastinal or bronchial glands, where they 
may involve the lung by extension or rupture. Still, again, the lymphatic 
channels may combine with the alimentary tract, and, as has been dis- 
cussed under Anthracosis and the Tubercle Bacillus, the organisms may 
reach the root of the lung by the lymphatic chain along the posterior 
midline of the body. This and the direct bronchogenic invasion form 
the principal infection tracts for Koch's bacillus. 

Bronchogenic Tuberculosis 

Larger masses of infective material inhaled in respiration may 
lodge in the bronchi or larger bronchioles and set up tuberculous ulcera- 
tions, from which smaller particles may be secondarily aspirated into 
the finer divisions of the bronchial tree. Such an occurrence, how- 
ever, is extremely rare. More commonly the tubercle bacilli are in- 
haled in a state of extreme dissemination, and are not arrested until 
they reach the point of division of the terminal bronchioles into the 
alveolar passages. One of two results may occur at this point: either 
there is set up a limited area of caseous or tuberculous pneumonia, 



568 



A TEXT-BOOK OF PATHOLOGY 



or the bacillus penetrates between the epithelial cells without pro- 
ducing a definite intra-alveolar lesion and causes specific tuberculous 
changes in the peri-alveolar and peribronchial connective tissues 
(miliary tubercles). It has been the occasion of some dispute among 
pathologists to decide which of these processes is most apt to arise when 
the infection occurs through the bronchial tubes. Undoubtedly, both 
kinds of change may take place, and it seems likely that in most 
instances there is a mixture of the two forms. When the infective 
material is in great abundance and is particularly virulent, and in cases 
in which the individual is especially vulnerable, caseous pneumonia 
predominates over the formation of tuberculous nodules. On the other 
hand, a less abundant infection or greater resisting power on the part of 
the individual determines a greater liability to the formation of nodules 
and less likelihood of extensive caseous pneumonia. Whichever lesion, 
however, is primary, the other soon becomes associated. Thus, if the 
epithelia of the alveoli are first affected with production of caseous 
pneumonia, the peri-alveolar connective tissues are soon involved, and 
' tubercles form in loco, or, by dissemination of the bacilli along the 
lymphatic channels of the peri-alveolar connective , tissues, tubercles 
appear at some distance from the first lesion. The alveoli contiguous 
to such secondary tubercles may in the next place become involved in 
caseous pneumonia. When the primary lesion is a tubercle in the peri- 
alveolar connective tissue, the adjacent alveoli in the same manner suffer 
caseous pneumonia. Thus, the disease spreads through neighboring 
lobules and in time affects considerable areas of the lung. 

Degenerative changes soon make their appearance. The areas of 
pneumonia, which began as small foci or as larger areas of lobular 
tuberculous pneumonia, change their color from a grayish to a yellow- 
ish color and become completely caseated ; while the secondary tubercles 
in the neighborhood, or those which were primarily formed, similarly 
become opaque and lusterless, and finally yellowish by caseation. The 
blood-vessels in caseous pneumonia or in the tubercles are inadequate 
to supply sufficient nourishment to the tissue. In the pneumonic areas 
this is due to proliferative changes in the intima and to direct pressure 
of the exudate, while in the tubercles it is due to hyaline and other forms 
of degeneration, with collapse of the walls. 

Coincidently with the process just described, round-cell infiltration 
and proliferative changes are manifest in the structures surrounding the 
diseased areas. In the case of the areas of caseous pneumonia, infiltra- 
tion and proliferation of the connective tissue of the septa, as well as 
proliferative changes in the blood-vessels of these parts, are observed. 
There is a wide variation in particular instances in the degree of these 
reparative processes, and in general it may be said that the more acute 
the disease, the more apt is degenerative caseation to take place and the 
less likely regeneration to occur. Similar overgrowth and infiltration 
may be seen around the tubercles, and in favorable instances the latter 
may eventually be completely encapsulated or converted into a fibrous 
nodule. In instances in which the reparative processes are very exten- 



DISEASES OF THE RESPIRATORY SYSTEM 



569 



sive there may eventually be a preponderance of connective tissue over 
caseous pneumonia or miliary tubercles. 

Varieties. — We may distinguish all of the forms of bronchogenic 
tuberculosis by the name of pneumonic tuberculosis, from the fact 
that the element of caseous pneumonia is always an important one, and 
separates them sharply from hemogenic and lymphogenic tuberculosis, 
in both of which the formation of miliary tubercles predominates over 
other processes. It must, however, be remembered that in some cases 
of hemogenic tuberculosis the lesion may take the form of a localized 
pneumonic tuberculosis by reason of the fact that the first-formed miliary 
tubercles are soon obscured by a more extensive pneumonic process. 

Three forms of pneumonic tuberculosis are met with: the acute, 
which is frequently spoken of as acute caseous phthisis, or galloping 
consumption; the chronic, which is also known as chronic ulcerative 
phthisis; and the form in which fibrous overgrowth predominates, and 
which is, therefore, known as fibrous or fibroid phthisis. While typical 
instances of these forms are quite distinct, there is no sharp dividing line 
separating the groups, and individual forms merge insensibly one into 
the other. 

Acute pneumonic tuberculosis is more common in children than 
in adults. Two elements play a part in its occurrence: first, a high 
degree of susceptibility; and, second, abundant infection with virulent 
bacilli. The latter may be derived from without the body by direct 
inhalation, or may come from the discharge of older caseous areas in 
the lungs which have broken into the bronchial tubes, or from some 
focus of tuberculosis in the upper air-passages. 

Pathological Anatomy. — This form of tuberculosis is lobular, but 
very frequently by confluence of the affected areas an entire lobe 
may be involved. Either the base or the apex may be first affected. On 
section the lung presents a more or less variegated appearance in the 
earlier stages, due to the formation of minute patches and lobular areas 
of caseous pneumonia having a grayish appearance, and the coincident 
congestion of surrounding portions of the lung tissue. Sections through 
the lung which cut a terminal bronchiole in a longitudinal direction show 
it more or less filled with cheesy exudate and surrounded by peri- 
bronchial caseation (Fig. 245). Transverse sections give the appearance 
of a section through a large tubercle or an aggregation of tubercles, but 
the lumen of the bronchiole may usually be discovered in the center or 
to one or the other side. Small miliary tubercles may be apparent in the 
edges of the pneumonic patches, and even for some distance around 
them, but the connective tissue involvement is more apt to appear 
as a diffuse infiltration along the peribronchial and perivascular lymph- 
atics than as distinct tubercles. As the process increases the lung tissue 
becomes more and more extensively involved and uniformly gray or 
yellowish and consolidated (Fig. 246). The cut section is generally 
somewhat granular in the earlier stages from admixture of fibrinous 
exudation in the alveoli; but later progressively increasing caseation and 
softening render the surface of section smooth and moist. Not infre- 



570 



A TEXT-BOOK OF PATHOLOGY 



quently complete destruction takes place and cavities are formed. 
These are usually small and present no marked tendency to the forma- 
tion of an organized wall, but appear simply as necrotic excavations 
with irregular, ragged outlines. The pleura over the surface of such 
a lung is usually inflamed and covered with more or less fibrinous or 
fibrinopurulent exudation, and not rarely with an abundant crop of 
tubercles. Sometimes a superficial lesion may rupture into the pleural 
cavity and cause pneumothorax or, later, pyopneumothorax. 

When the process is less active 
and the infection less abundant, con- 
fluence of the lobular areas is less 
likely to occur, and there are seen 
merely disseminated patches of cas- 
eous pneumonia scattered through 
various parts of the lung, which is, in 
general, more or less congested. In 
such instances, too, the evidences 
of reparative change are more de- 
cided. Complete encapsulation with 
subsequent calcification may ensue, 
or fibrous overgrowth mav convert 






Fig. 245. — Bronchogenic tuberculosis of 
the lung, showing the involvement of the 
tissues surrounding the terminal bronchioles 
(Birch-Hirschfeld). 



Fig. 246. — Extensive bronchogenic 
tuberculosis (caseous pneumonia) of the 
base of the lung (Orth)). 



the entire area into a cicatricial mass. If the cheesy area is simply en- 
closed with fibrous tissue, it may remain quiescent for a time, possibly 
for years, and subsequently penetrate the enclosing wall and occasion 
a fresh extension of the whole process. 

Chronic pneumonic tuberculosis is the ordinary form of pulmonary 
phthisis. It begins in the apices of the lungs in the great majority 
of cases, though children are as likely to be first affected at the bases 
as at the apices. The apices present areas of low resistance because of 
their short excursion of motion and the slow gaseous interchange. 
They are slightly less vascular than lower lung portions. 



DISEASES OF THE RESPIRATORY SYSTEM 



571 



While there is no doubt that chronic phthisis is usually due to infec- 
tion through the inspired air, it must be admitted that occasionally the 
onset of the process is due to infection through the blood or lymphatic 
channels (see p. 566). In the instances of the latter kind there may 
first be established a localized lesion which caseates and penetrates a 
bronchial tube, discharging its contents, and thus leading to widespread 
bronchogenic infection. The further 
development of the disease takes 
place in several distinct ways (see 
below) . 

Pathological Anatomy. — When 
there has been a pre-existing bron- 
chitis, adhesion of the bacilli may 
occasion tuberculous bronchitis with 
ulceration and secondary involve- 
ment of the surrounding tissues. 
More commonly the bacilli lodge 
in the finer bronchioles or alveo- 
lar passages, as in acute pneu- 
monic phthisis, and give rise to 
lobular areas of caseous pneumonia, 
surrounded by tubercles which are 
formed along the course of the 
lymphatic vessels leading out from 

the first-formed CaseOUS foci. There Fig . 247.— Tuberculous cavity of apex 

is a tendency to a Constant in- of lun S communicating with bronchus, as 

» , <■ v 1 j_i shown bv rod (from a specimen in the col- « 

crease of the area of disease by the lection of Dr. Alien J. Smith), 
discharge of caseous material into 

contiguous bronchi and its aspiration into other parts of the lung, and 
also by dissemination of the infection along the lymphatic vessels 
traversing the connective tissue around the blood-vessels and bronchi. 
Section through the lung discloses more or less consolidated tissue of an 
opaque, grayish or yellowish appearance, in which the bronchi may be 
seen as open spaces or filled with mucopurulent liquid. Little distinc- 
tion between caseous pueumonia and the tubercles can be made in the 
center of such an area, but at the edges, where the process is seen in the 
earlier stages, such distinction may be possible. 

At times areas of a fibrinous or cellular pneumonia are formed. 
These differ from caseous pneumonia in presenting a granular or gelat- 
inous appearance, and in their liability to partial or complete resolu- 
tion. The process is serofibrinous and cellular in character, and often, 
though not always, due to secondary infections. 

The same tendencies to degeneration and softening, on the one 
hand, and to the processes of repair, on the other, are seen in chronic 
pneumonic phthisis as are apparent in the acute form. There is the 
difference, however, that these changes are less rapid, and that, as a 
rule, proliferation of connective tissue with the formation of fibrous 
tissue is more pronounced than in the acute disease. 




572 



A TEXT-BOOK OF PATHOLOGY 



The degenerative and necrotic processes lead to a most characteris- 
tic lesion of tuberculous lungs— the cavity (Fig. 247) . Cavities are formed 
either through the dilatation of the bronchioles (bronchiectasis), due to 
their ulcerated and weakened condition and to the pressure of retained 
secretions, with subsequent ulceration and breaking down of the sur- 
rounding caseous tissue; or, on the other hand, to liquefaction of caseous 
areas not in connection with a bronchial tube. In the latter case, how- 
ever, communication with the bronchi is frequently established by ex- 
tension. A single cavity may grow larger and larger by constant ulcera- 
tive processes, in which not alone the caseous tuberculous degeneration 




Fig. 248. — Chronic phthisis pulmonalis with cavities of left lung; note communicating 
cavities near apex, disseminated miliary tuberculosis of right lung (from a specimen in the 
collection of Dr. G. W. Norris). 

takes a part, but also active ulcerative changes dependent upon mixed 
infection through inspiration of pyogenic organisms. As a rule, how- 
ever, larger cavities are formed by the confluence of separate smaller ones, 
and there may be found a series of excavations communicating more or 
less extensively with each other (Fig. 248). The cavity, or vomica, con- 
tains a variable amount of ill-smelling, putrid secretion, consisting of 
broken-down cheesy matter, pus-cells, degenerated epithelial cells 
and fibers of elastic tissue, and containing tubercle bacilli, pyogenic 
organisms, and occasionally mould fungi. The walls of the cavity are 
generally formed by reparative fibrous proliferation, and are covered 



•DISEASES OF THE RESPIRATORY SYSTEM 



573 



with a "pyogenic membrane," usually darkly pigmented. The inner 
surface is very rough and ribbed by projecting bands. The latter 
represent the trabecular and blood-vessels of the lung tissue, which have 
resisted ulceration more obstinately than the surrounding structure of 
the lung. This resistance may continue to such an extent that the 
blood-vessel is left as a cord passing directly through the center of the 
cavity; but, as a rule, the lumen of the vessel is soon obliterated by 
thrombosis and the vessel itself destroyed. Not infrequently examina- 
tion of the blood-vessels in the wall of the cavity or passing through it 
show small aneurysmal dilatations which result from the weakening of 
the wall by the surrounding necrotic process and from the pressure of 
the blood within. It is from aneurysms of this character that the large 
and often fatal hemorrhages of the later stages of tuberculosis take place, 
though hemorrhage may also occur directly from erosion of blood-ves- 
sels without aneurysmal dilatation. The smaller hemorrhages of the 
early stages of phthisis, which occasion only a streaking of the sputa 
with blood, are due to early erosion of small vessels of the bronchioles 
or to capillary ruptures dependent upon congestion. 

The reparative processes (connective-tissue formation) in chronic 
pneumonic tuberculosis may cause cessation of the disease when only 
limited areas of the lung are affected, by surrounding and thus encap- 
sulating the diseased parts, or by complete fibrosis of the areas. These 
changes are dominant in the form next to be described. 

Fibroid Phthisis. — The reparative or fibrous processes which tend 
to counteract caseation and destruction may begin before cavity forma- 
tion or after it. When beginning in the earlier stages the caseous areas 
will be found to present a capsule of more or less well-developed fibrous 
tissue, which may completely surround and separate them from the 
neighboring tissue of the lung. The capsule tends to contract and 
shrink, and the caseous material within may become completely cal- 
careous. In this manner a limited focus of tuberculosis of the lungs not 
infrequently becomes completely arrested. When the capsule is not so 
firm, after a period of quiescence or latency extending over even a 
number of years, fresh extension may begin, the capsule may be per- 
forated, and acute pneumonic phthisis may be established, or the tuber- 
culous process may extend more slowly through the contiguous areas 
as chronic ulcerative phthisis. When the tuberculous lesion is limited 
and consists of minute foci not too closely conjoined, the fibrous tissue 
proliferation may intersperse the lesion so that the whole is converted 
into sclerotic tissue instead of being merely surrounded by a capsule. 

The fibrous capsules surrounding the cavities, which have already 
been alluded to, may be of varying prominence. In case of small 
vomica? with pronounced fibrous walls the contraction of the latter may 
almost obliterate the cavities, leaving only narrow and distorted spaces 
containing a small amount of putrid material (cicatrices fistuleuse of 
Laennec). Complete healing of a cavity of notable size probably never 
occurs. When the excavations are of large size the reparative processes 
consist simply in the formation of a thick wall of fibrous tissue, which 



574 



A TEXT-BOOK OF PATHOLOGY 



prevents the further extension, for a time at least, of the tuberculous 
process. 

Complications in Bronchogenic Pneumonia. — Of first importance 
in tuberculosis of the lung is the condition of the pleura. In the acute 
pneumonic form the pleura adjoining the diseased areas is generally 
more or less inflamed and may present considerable fibrinopurulent 
exudation, as in croupous pneumonia. Serous or seropurulent exuda- 
tion may likewise be present, and eruption of miliary tubercles in the 
pleura is not unusual. The same processes may occur in chronic pneu- 
monic tuberculosis or chronic phthisis. More commonly there are found 
simply fibrous adhesions binding the one surface of the pleura to the 
other, especially at the apex. 

Extension of the tuberculous process may also take place directly 
upward along the air-passages, and is due, for the most part, to direct 
infection by the sputa. There may thus occur tuberculous ulceration 
of the larger bronchi, of the trachea, of the larynx, or of the pharynx. 
When the sputa are swallowed, as is especially likely to happen in 
children, or in adults during sleep, intestinal tuberculosis is apt to occur. 

Finally, dissemination of the tuberculous disease through the 
blood is frequent. A caseous area adjacent to one of the veins 
may penetrate the lumen of the vessel and discharge its contents into 
the circulating blood, or may first occasion tuberculous proliferation in 
the intima of the vein or infectious thrombosis, from which the blood is 
secondarily infected. There results general miliary tuberculosis, the 
tubercles occurring especially in the spleen, the liver, the kidneys, the 
choroid coat of the eye, or in the membranes of the brain or other serous 
membranes. 

Acute pneumonia may accompany either acute or chronic pneu- 
monic tuberculosis, and certain authors insist that in practically all 
cases there is more or less mixed infection. This is probably not the 
case, but complicating pneumonia is undoubtedly frequent. In most 
of such cases localized patches of catarrhal bronchopneumonia are seen 
between the caseous lobules; but sometimes a frank fibrinous consolida- 
tion may occupy the lower lobe of a lung in which the upper lobe pre- 
sents beginning tuberculosis. Quite frequently there are small areas 
of pneumonic consolidation of fibrinous character in the lobe which is 
itself the seat of tuberculous involvement. Toward the end of life there 
is usually extensive edema of the bases and posterior portions of the 
lungs. 

The heart has interesting relations with tuberculosis of the lungs. 
Early writers called attention especially to the fact that phthisical sub- 
jects frequently present unusual smallness (hypoplasia) of this organ, 
and later attention was directed to the fact that congenital stenosis 
of the pulmonary orifice predisposes to tuberculosis of the lungs. Some 
have claimed that there is an antagonism between cardiac disease and 
tuberculosis. This view is not well founded, though it is probable that 
the chronic congestion of cardiac disease renders the lung somewhat 
less vulnerable to tuberculous infection than the normal lung. Where 



DISEASES OF THE RESPIRATORY SYSTEM 



575 



there is a long-standing tuberculous consolidation, hypertrophy, espe- 
cially of the right ventricle, is likely to occur. Tuberculous pericarditis 
may be found in association with tuberculous pleurisy; and tubercles 
may also, though much more rarely, be found upon the endocardial 
lining. The latter are due to infection through the blood. 

Hematogenic Tuberculosis 

This form occurs when a focus of tuberculous disease ruptures into 
a blood-vessel and the infective contents are disseminated in the cir- 
culation. As a rule, hemogenic tuberculosis of the lungs is only a part 
of a general tuberculosis of the entire body. The points from which 
the primary infection may take place are, of course, numerous, but 
caseous lymph-glands of the cervical or peribronchial group, or old. 
foci of tuberculosis at the apex of the lung, are perhaps the most fre- 
quent. The organs and structures of the body likely to be involved 
by general hemogenic tuberculosis are the spleen, the liver, the kidney, 
the choroid coat of the eye, the meninges, and, more prominently than 
any other organ, the lungs. In the rare cases in which rupture of an 
old pulmonary focus has occurred into one of the branches of the pul- 
monary artery, only one lung, or but a part of a lung, may be involved. 
Some writers think that intimal tubercles of the pulmonary artery and 
its branches are the sources of continued infection of the lungs. Atten- 
tion has been previously directed to the probability that in some, if not 
many, cases what appears to b*e bronchogenic pulmonary tuberculosis 
is, in reality, hemogenic, the bacilli having entered the body at some 
obscure point without causing a lesion at the portal of entrance, and 
having produced a localized lesion in the lung instead of the more typical 
disseminated tuberculosis usually found in hematogenous infections. 

Pathological Anatomy. — The pathological feature of importance 
in hematogenic tuberculosis is the formation of miliary tubercles. 
These appear as gray or translucent areas, the size of millet seeds, around 
and involving the terminal arterioles or capillaries in the intervesicular 
septa. At first they may be so small that the naked eye scarcely dis- 
covers them, and they are so translucent that oblique light is necessary 
to make them appear to view. Later, they increase in size and become 
more grayish and opaque. Microscopically, there are the well-known 
characteristics of the miliary tubercle embedded in the perivascular 
connective tissue. These tubercles, however, are prone to distinguish 
themselves from the characteristic tubercles seen elsewhere by their 
more irregular outline and the more irregular arrangement of their com- 
ponent histological elements. When the tuberculous process is particu- 
larly rapid and virulent, giant cells are few in number, and the tubercle 
is composed mainly of proliferated connective-tissue cells of the ordi- 
nary type, some epithelioid cells, and round infiltration cells, all of 
them more or less granular, and the entire nodule surrounded by a zone 
of caseous, catarrhal, or even hemorrhagic pneumonia of the contiguous 
alveoli of the lung (Fig. 249). The tubercles are rarely seen in the stage 



576 



A TEXT-BOOK OF PATHOLOGY 



of advanced necrosis, but this may take place in instances of a more 
chronic course in which the bacteria are admitted to the lungs slowly 




Fig. 250. — Hematogenic tuberculosis, showing many scattered miliary tubercles and 
several clusters (modified from Bollinger). 



and perhaps in a state of lesser virulence than common. In those in- 
stances of what may be termed "chronic miliary tuberculosis" there may 
be a considerable amount of caseation of the tubercles, and the patches, 



DISEASES OF THE RESPIRATORY SYSTEM 



577 



as a rule, become decidedly larger than in the ordinary acute form (Fig. 
250). An explanation of this form of chronic miliary tuberculosis has 
been offered by certain authors, who hold that these are instances of in- 
fection through the thoracic duct and blood-vessels. The infective 
material enters the thoracic duct from caseous lymphatic glands in the 
abdomen or thorax, and is discharged with the lymph into the veins in 
a gradual manner, only a little being allowed to pass at a time. 

The ordinary and typical acute miliary tuberculosis presents itself 
clinically as an acute infectious disease, running its course rapidly and 
causing early dissolution. The disease is rather a general toxemia than 
a local process, and toxemic changes may be present in various organs, 
such as occur in other infectious and toxemic diseases. The heart, liver, 
the kidneys, and, in general, the parenchymatous structures are prone 
to become degenerated, and when the febrile infection continues there 
may be extensive fatty degeneration. In addition to the eruption of 
miliary tubercles in other organs, to which allusion has already been 
made, there is also involvement of the pleura which belongs properly to 
the pulmonary process itself, and is simply a continuation of the same 
infection which gave rise to the pulmonary involvement. 

Lymphogenic Tuberculosis 

It is possible for tuberculous infection of the lungs to occur through 
the lymphatic channels in several ways. In speaking of acute miliary 
tuberculosis, particularly of the more gradual type, reference was made 
to the fact that infective material is sometimes carried by the thoracic 
duct from the lymphatic glands of the abdomen and posterior medi- 
astinum, as well as possibly from carious thoracic vertebrae to the blood- 
vessels, and thence distributed through the blood to the lungs as a hema- 
togenic infection. Direct infection, however, through the lymphatic 
channels may take place. Thus, tuberculous pleuritis, either primary or 
secondary to tuberculous disease of the vertebrae or ribs, sometimes 
spreads directly into the lung through the lymphatic vessels traversing 
the interlobular connective tissue; and in cases of caseous tuberculosis 
of the peribronchial glands the infective material may be conveyed into 
the lungs either by a reversal of the current of lymph in the vessels run- 
ning to these glands or by direct extension along the lymphatic walls. 
A form of lymphogenic tuberculosis of the lungs may also be referred to 
in which caseous lymph-glands directly perforate the lung tissue, but 
the actual dissemination of the process in the lungs in these cases is 
usually through the bronchial tubes into which the bacilli gain entrance. 

Pathological Anatomy. — It is characteristic of lymphogenic tuber- 
culosis to find small nodular areas which microscopically are seen to be 
more or less characteristic . tubercles. These are scattered along the 
lymphatic vessels running in the interlobular septa or surrounding 
the blood-vessels and bronchi. In the instances of lymphogenic tuber- 
culosis secondary to pleuritis suppurative lymphangitis and perilymph- 
angitis (see Pneumonia) are not infrequently associated. 

37 



578 



A TEXT-BOOK OF PATHOLOGY 



SYPHILIS 

It has been the occasion of much dispute whether the many forms 
of pulmonary disease attributed to this cause can be really so classified. 
Among such doubtful cases are certain pulmonary consolidations in 
secondary syphilis, and lesions of the lungs in old syphilitics that have 
the superficial appearances of tuberculosis. Undoubtedly some of 
the conditions attributed to syphilis are cases of tuberculosis, or of 
some other form of pulmonary disease. But there are other varieties 
which can unquestionably be spoken of as syphilitic. Among these are 
the diffuse infiltration of the newborn and the tertiary gummata. 

Diffuse syphilitic infiltration of the lungs is occasionally met 
with in the newborn. As a rule, infants showing this are stillborn. 
It manifests itself as a more or less lobar consolidation and induration 
of the lung tissue. On section, the lung is light gray or almost white in 
color, and completely airless, so that the name pneumonia alba, given 
by older writers, was highly significant. Microscopically, there are 
seen widespread round-cell and spindle-cell infiltration and prolifera- 
tion in the interalveolar and interlobular connective tissues, with more 
or less compression of the bronchioles and alveoli. The epithelium of the 
latter may be somewhat proliferated and desquamated, and shows a 
tendency to fatty degeneration and necrosis. In some instances the de- 
generative changes do not take place, and the proliferated epithelium 
of the alveoli is massed within the alveolar lumen, and is, for the most 
part, of a cuboidal character. The blood-vessels commonly show 
proliferation of the adventitia as well as of the intima, and may be 
completely obliterated. According to Birch-Hirschfeld, syphilitic fe- 
tuses of the sixth or seventh month sometimes present limited disease 
of this nature, and of such distribution that it is recognized to begin 
as a peribronchial and peri-alveolar infiltration of lobular distribution. 
In this type Spirochete pallida are very numerous. 

Syphilitic gummata may be associated with the diffuse form of 
congenital syphilis, or may be present in the newborn without the 
latter. Gummata are occasionally seen in adults. They are present 
most frequently near the root of the lung beneath the pleura, but 
may be scattered through other parts of the organ. As a rule, the 
number is limited. They appear as more or less rounded nodules of a 
grayish to yellowish color, with more or less fibrous overgrowth sur- 
rounding them and often radiating from them into the surrounding 
lung tissue. Central necrosis may proceed to such extent that cavities 
are formed. 

Occasionally the contents of a gumma may be discharged through 
the bronchial tubes, or they may be absorbed and a cicatricial pucker- 
ing of the lung tissue may mark the place of the former disease. Spiro- 
chetal pallida' can be found, but are not numerous. 

Syphilitic fibrous induration of the lung, so-called, has been 
described, and it seems likely that some of the cases embraced in the 
description are really syphilitic in nature. The process begins, as a rule, 



DISEASES OF THE RESPIRATORY SYSTEM 



579 



at the root of the lungs, from which it radiates through the tissue toward 
the pleura. The fibrous tissue, for the most part, surrounds the bronchi 
and blood-vessels (Fig. 251). In another group of cases the process 
spreads from the pleura and occasions the formation of dense bands of 
fibrous tissue passing inward into the lung structure. In still other 
cases the fibroid overgrowth is so diffuse that the appearance presented 
resembles so closely that of pneumonokoniosis that is is practically in- 
distinguishable. It is quite probable that many instances in which 
appearances such as these are met with are not at all syphilitic; but 




Fig. 251. — Syphilis of lungs: a, a. Thickened alveolar walls or stroma; b, partly longi- 
tudinal section of bronchus; c, uninfiltrated alveoli; d, new connective tissue infiltrated 
with small round cells; e, cells lining alveoli; /, artery showing thickened walls; g, des- 
quamated lining cells (Linsley). 

« 

the occurrence of changes of this description in association with gum- 
mata, and, again, the occurrence of such changes without gummata in 
undoubtedly syphilitic individuals, make it likely that some at least are 
of this origin and nature. Spirochcetce pallidce are exceedingly difficult 
to find, and only can be found, indeed, where there is a frank infiltrate 
among the fibrous tissue. 

GLANDERS 

Glanders occasionally affects the pulmonary tissue, the infection 
taking place either by inhalation from ulcerated lesions in the nose 
or other portions of the upper air-passages, or, more rarely, by distribu- 



580 



A TEXT-BOOK OF PATHOLOGY 



tion of the bacilli through the blood. The lesions are of two kinds. 
There may be merely a grayish or purulent infiltration of a diffuse 
character, with the formation of abscesses and often with associated 
hemorrhagic infiltration. Considerable areas of the lung may be con- 
solidated in this manner, or the process may be localized and lobular. 
In other cases nodular patches varying from the size of a hemp-seed to 
that of a pea are seen in various parts of the lung. These consist of 
masses of round cells, and show an early tendency to degeneration. 
More or less hemorrhagic and catarrhal inflammation of the alveoli sur- 
rounding these nodules may be present. 

ACTINOMYCOSIS 

Actinomycosis is a rare affection of the lungs. It may result from 
the direct extension of actinomycosis of the lymphatic tissues and 
cellular structures in the anterior or posterior mediastinum, when there 
are formed in the pulmonary tissue fistulous necrotic tracts containing 
more or less cheesy and purulent material, in which the characteristic 
yellowish actinomycosis granules are found. The latter, on microscopical 
study, show the actinomyces. The infection may also take place by a 
gradual descent of the process from the mouth or upper respiratory 
passages along the trachea and bronchi to the lung; or, more commonly 
still, by aspiration of the infective agents. In the latter cases nodules 
consisting of round cells are formed, and present themselves as grayish 
or grayish-red patches varying in size from that of a pea to that of a 
cherry, and showing a decided tendency to fatty degeneration and 
purulent softening. The surrounding lung tissue is commonly con- 
solidated, and presents the appearances of purulent and catarrhal or 
even hemorrhagic pneumonia. In many cases there is also a manifest 
tendency to productive changes, which lead eventually to the formation 
of more or less fibrous tissue within the alveoli and in the interalveolar 
and interlobular connective tissues. Not rarely this indurative process 
completely surrounds areas of degeneration and softening. Infection 
with streptothrix follows the same general character. 

TUMORS 

The lungs are, comparatively speaking, rarely the seat of tumors, 
though a variety of both primary and secondary growths occur. 

Connective=tissue Tumors. — Small nodular fibromata have occa- 
sionally been observed scattered through the lungs in the peribronchial 
connective tissue, and a few instances of similar nodules of lipoma 
are recorded. Chondroma is more common than either of these, and 
doubtless takes origin from the bronchial cartilages. Secondary chon- 
dromata have been observed in cases of chondroma elsewhere. True 
osteoma is rare, but more frequently ossification of sclerotic areas is 
met with in instances of pneumonokoniosis. 

Sarcoma is the most frequent connective-tissue tumor of the lungs. 



DISEASES OF THE RESPIRATORY SYSTEM 



581 



The lymphosarcoma form may originate in the lymphatic glands sur- 
rounding the bronchi at the roots of the lungs, from the lymphatic 
nodes surrounding the smaller bronchi within the lungs, from the 
lymphatic vessels themselves, or from the subpleural or other con- 
nective tissue of the lung itself. Primary sarcoma is less common than 
secondary. In one form it presents itself as rounded masses of grayish 
or yellowish color lying around the bronchi in the root of the lung (Fig. 
253). On section through this it is seen to consist of more or less en- 
larged and transformed lymphatic glands, and there may be secondary 
nodules scattered through the lung. This 
form of sarcoma is particularly common in 
pneumonokoniosis, as seen in the fibroid 
lungs of the cobalt-miners of Schneeberg. 
Primary sarcoma may also be of the form 
called endothelioma, arising either within 
the lung tissue or from the pleura. The 
lymphatic vessels in the peribronchial tissue 
become filled with proliferated cells, and 
their ramification may be distinctly visible 
on section as a network traversing the pul- 
monary tissue. Primary sarcoma of the 
spindle-cell or round-cell variety may spring 
from the subpleural connective tissue. 
Giant-cell sarcoma has been observed. 

Secondary sarcoma is extremely common. 
It is seen in nearly all instances in which 
metastasis has occurred from a primary 
growth in any part of the body. In these 
cases there are found well-defined nodules of 
varying size, situated for the most part 
near the surface of the lung (Fig. 254). 
They are whitish in color and tend to soften. 
The lung tissue between may be congested , 
and there may even be pneumonic con- 
solidation. Secondary sarcoma of the lung 
may also occur from direct extension of 
mediastinal sarcoma or of sarcoma in other 
of the surrounding structures. An interest- 
ing type of secondary involvement of the 
lungs by sarcoma or a process resembling sarcoma occurs in "malig- 
nant lymphoma" or "lymphadenoma," either with or without leu- 
kemia. -These may be considered as allied to generalized lympho- 
sarcoma. The lungs are found to contain small nodules, consisting of 
round cells without stroma or embedded in a more or less reticular 
matrix of stellate and spindle cells. 

Epithelial Tumors. — Carcinoma is practically the only form to be 
considered, though adenoma of the lung has been described. Carcinoma 
of the lung is certainly less frequent than was formerly believed, sarcoma 




Fig. 252. — Sarcomatosis of 
lung, hematogenous in origin, 
showing distribution from hilus. 



582 



A TEXT-BOOK OF PATHOLOGY 






Fig. 254. — Secondary sarcomata of the lung: the primary growth was attached to the 

pleura. 



having been confused with it. Massive cancer may start from the 
mucous glands of the larger bronchi near the root of the lung. The 



DISEASES OF THE RESPIRATORY SYSTEM 



583 




Fig. 255. — Secondary metastatic lymphosarcoma of lung (from a specimen in the collection 

of Dr. Allen J. Smith). 




Fig. 256. — Metastatic carcinoma of lungs from a primary pyloric growth (photograph by 

Dr. Ayer). 

tumor is irregular, soft, and tends to ulcerate in the center, forming 
cavities. Secondary nodules within the lung tissue are seen along the 



584 



A TEXT-BOOK OF PATHOLOGY 



lymphatic vessels surrounding the bronchi. Primary carcinoma may 
also start from the epithelium of the finer bronchial tubes. The pro- 
liferation soon penetrates the wall of the bronchus and extends along 
the lymphatic vessels in the peribronchial connective tissue. In this 
manner bands of new growth are seen traversing the lung. Occasionally 
squamous-celled carcinoma may originate in the epithelium of the 
terminal bronchioles and alveoli. 

Secondary carcinoma of the lungs is less frequent than secondary 
sarcoma. It may occur by metastasis from cancer elsewhere, and in 
these instances the appearance of the nodules is much the same as that 
of sarcoma. Secondary cancer of the lung may also result from exten- 
sion of esophageal carcinoma or of cancer of the breast penetrating the 
thoracic walls and pleura. Finally, in carcinoma of the upper respira- 
tory passages or of the mouth, inhalation of cancerous particles may 
lead to secondary nodules in the lungs, associated at times with areas 
of bronchopneumonia. 

Cysts. — Congenital cysts have been described, but they are probably 
merely dilatations of the bronchi. (See Bonchiolectasis.) Adeno- 
matous proliferation of the epithelial lining of such dilatations may 
take place. Dermoid cysts are rarely encountered. They may dis- 
charge through the bronchial tubes. 

PARASITES 

Besides the specific and pathogenic micro-organisms that have been 
referred to as occurring in tuberculosis, pneumonia, and other infec- 
tious diseases, various forms of bacteria and mould fungi are met with 
as accidental and non-specific parasites. Such micro-organismal collec- 
tions are most frequent in areas of gangrene, in degenerated infarcts, 
and in dilated bronchi or tuberculous cavities. Sarcinae, leptothrices, 
streptothrices, and several varieties of aspergillus have been noted. The 
general term Pneumonomycosis aspergillina is applied to the occurrence 
of the last-named mould fungi in the lungs. Sometimes they are so 
abundant that they are readily discovered in the sputa; and it is likely 
that certain inflammatory conditions of the lungs are directly due to 
such organisms. The clinical course may suggest tuberculosis, and 
pathologically diffuse or irregular consolidation of the lungs may char- 
acterize such cases. (See p. 324.) 

Animal Parasites. — Of the lowest forms of animal life or protozoa, 
the Monas lens, cercomonas, and Paramecium have been observed. 
These are entirely accidental, occurring in cases of gangrene, putrid 
bronchitis, and similar conditions. The class of Vermes furnishes the 
more important parasitic affections of the lungs. The Paragonimus 
westermanii is not infrequent in parts of Asia. It occasions serious 
hemoptysis. The Strongylus apri, echinococcus cysts, and Cysticercus 
celhtlosa 3 are occasionally seen. Lingnatula rhinaria has been observed. 



DISEASES OF THE RESPIRATORY SYSTEM 



585 



The Pleura 

Anatomical Considerations. — The pleura is a membrane composed 
of fibrillar connective tissue and elastic fibers, containing a rather abun- 
dant network of capillaries. It is lined on the surface with a single layer 
of flat endothelial cells, between which there are openings from the 
pleural cavity into the subpleural lymphatics. The latter form a rich 
network in the subpleural connective tissue and play an important part 
in the pathological processes affecting the pleura. It must be remem- 
bered that the two pleural surfaces are normally in apposition, that is, 
no cavity exists. They move over one another with the movements of 
the chest. 

CIRCULATORY DISTURBANCES 

Active Hyperemia. — This arises as the early stage of inflamma- 
tion or as the result of decrease in tension, such as occurs when fluid 
in the cavity is removed. 

Passive hyperemia occurs in various diseases interfering with the 
respiration, and still more intensely in cases in which there is pressure 
upon the azygos veins or diffuse intrathoracic pressure. 

Petechial hemorrhages may occur when the congestion is intense. 
They are particularly frequent and prominent in cases of death from 
suffocation, but are also seen in various disorders of the blood and 
hemorrhagic diatheses, such as pernicious anemia, purpura, and in- 
toxications of various kinds. 

Hemothorax is the term applied to the presence of free blood in the 
pleural cavity. It may be due to wounds of the chest wall, causing 
rupture of blood-vessels, to fracture of the ribs, and to rupture of 
aneurysms into the pleural sac. In some cases the etiology is obscure. 
If the pleura is in a healthy condition and secondary infection does 
not take place, more or less rapid absorption of the blood ensues. When 
infection occurs, secondary inflammations of the pleura and disorganiza- 
tion of the blood result. 

Hydrothorax, or dropsy of the pleural cavity, may be but a part 
of a general edema occurring in chronic kidney or heart disease. It 
is usually bilateral, and the fluid presents the ordinary characteristics 
of a serous effusion. Unilateral hydrothorax is, however, not infre- 
quent in cardiac disease attended with great enlargement of the organ. 
The hydrothorax in such cases is generally right sided, and is probably 
due, according to Fetterolf and Landis, to pressure by some dilated 
segment of heart upon the pulmonary veins which drain those from the 
visceral pleura. The pleura itself is not particularly disordered, but 
very frequently some opacity and loss of luster is noted, and there may 
be edema of the subpleural fibrous tissue. The lungs are pressed back- 
ward toward the root and against the spinal column, and may be con- 
siderably compressed. Unilateral hydrothorax may be due to pressure 
upon the veins of one side by tumors or aneurysm. A small amount of 
serous outpouring into the pleural sacs occurs quite commonly just 



586 



A TEXT-BOOK OF PATHOLOGY 



prior to death. The fluid of hydrothorax has the usual characters of 
transudates, low specific gravity, pale color, alkalinity, moderate pro- 
tein content, and very low cell content. 

Chylous effusion in the pleurae is due to obstruction or rupture of the 
thoracic duct or some large lymphatic channel, with the appearance 
of a milky opaque fluid containing fat-droplets. 

Hydrothorax causes compression of the lungs and displacement of 
the other adjacent viscera. The seriousness of the results are in pro- 
portion to the amount of effusion. 

Pneumothorax designates the presence of air in the pleural cavities. 
It may result from rupture of tuberculous vomica?, gangrenous areas, 
softened hemorrhagic infarcts, or abscesses of the lungs, or rupture of 
emphysematous air-vesicles beneath the pleura, allowing egress of air 
into the pleural sac. It may also occur after an empyema has ruptured 
into the lung and established a fistulous communication between the 
pleural sac and the bronchioles. Very rarely it is due to a penetrating 
wound of the chest. The pleural sac may be more or less tensely 
distended with air; the lung collapses against the spine, is more or 
less grayish or brownish in color, indurated, and airless. The pleura 
itself may present no abnormality, and the air may be absorbed; but 
very frequently infection takes place, and purulent exudation from the 
pleura collects in the sac. The condition is then spoken of as pyopneumo- 
thorax. The neighboring organs are often greatly displaced, particularly 
the heart, the diaphragm, and the liver. In left-sided pneumothorax 
the heart may be pushed far to the right of the sternum, and when the 
right side is affected the liver may be pushed downward considerably 
below the ribs. The condition of the air inlet and outlet has some- 
thing to do with the outcome of the condition. If the fistulous channel 
from a lung cavity permits air only to pass to the pleura with inspira- 
tion, and does not permit its escape upon expiration, the accumulation 
will continue. The air, once within the cavity, may remain in about the 
original amount, or it may undergo variations when a free ingress and 
egress is afforded. Pneumothorax may be circumscribed by pleural 
adhesions, and then is termed "closed." 

INFLAMMATION 

Inflammation of the pleura, or pleuritis, is designated by the 
clinical name pleurisy. 

Etiology. — It may result from local or from general causes. Among 
the local causes the most important are extension of inflammation 
from the lungs in the various forms of pneumonia, in gangrene and tuber- 
culosis; extension from pericarditis or mediastinal diseases, and extension 
from inflammatory affections of the spine, of the ribs, or of the chest 
walls. Less directly, peritonitis, hepatic abscess, and other abdominal 
affections may occasion pleuritis by extension, and in rare cases perfora- 
tion of esophageal or gastric ulcers, or abscess of the spleen or liver, 
may be the cause. 



DISEASES OF THE RESPIRATORY SYSTEM 



587 



In the group of cases due to general causes the pleural inflamma- 
tion is the result of infection or intoxication involving the pleura through 
the blood. Thus, in pyemia and septicemia, in rheumatism and in 
other acute infectious diseases, and in Bright's disease, acute inflam- 
mation of the pleura is not uncommon. Cold and traumatism have 
long been regarded as important causes, but their action is doubtless 
only a predisposing one, the immediate cause being some infection for 
which the traumatism or the exposure to cold has paved the way. 

It is to be remembered that the pleura is made up of a visceral and a 
parietal layer, two smooth surfaces bathed by a small quantity of lymph, 
sliding over one another in respiratory movements. While the incep- 
tion of pleurisy may be localized the process soon spreads over both 
surfaces. It is, of course, possible to have an acute or chronic pleurisy 
localized by reactive connective-tissue growth, as when due to a purely 
local cause, such as an indented broken rib. 

The micro-organisms found in pleurisy are quite numerous. In the 
cases secondary to ordinary pneumonia, pneumococci are frequently 
discovered, and these micro-organisms may be present even though 
there be no pneumonia at all. In the instances secondary to tubercu- 
losis of the lungs, as well as sometimes in cases of primary pleurisy 
without affection of the lungs, tubercle bacilli are discovered. It is 
important to note the fact that in many instances a small and unrecog- 
nized tuberculous lesion of the lung may be the source of infection in 
cases which seemingly are primary pleurisies due to exposure, cold, etc. 
It would, however, be a mistake to assume that all of such apparently 
primary pleurisies have a tuberculous etiology. In the purulent cases, 
as well as in some instances of simple fibrinous or serofibrinous pleurisy, 
staphylococci and streptococci are detected. When there is abundant 
liquid it is always difficult to discover the micro-organisms, and in 
many instances in which bacteria have not been found it is probable 
that the difficulty of their demonstration, even by animal experimenta- 
tion, rather than their absence, accounts for the failure to demonstrate 
them. In rare instances the Bacillus coli communis, the typhoid bacil- 
lus, the bacillus of anthrax, and other organisms have been found. 

Pathological Anatomy. — Several forms of pleuritis may be recog- 
nized, though one of these merges into the other, and a single case 
may pass from one into another form at its various stages. It is well, 
however, to separate these stages as distinct forms, since many cases 
maintain a uniform character throughout. The forms are the fibrinous, 
serofibrinous, purulent, and hemorrhagic; after any of these forms there 
may be left chronic pleural thickening or adhesions of a fibroid char- 
acter. 

Fibrinous pleuritis begins with congestion and loss of luster of the 
pleural surface, after which there soon follows exudation of a fibrinous 
character, forming a thin, whitish pellicle on the surface. This may be- 
come yellowish and increase in thickness, so that the pleural surfaces 
become agglutinated, and when separated present an appearance lik- 
ened to the appearance of two pieces of buttered bread separated after 



588 



A TEXT-BOOK OF PATHOLOGY 



having been pressed together (bread-and-butter pleurisy). This process 
may be confined to small areas of the pleura, or it may be quite universal. 
Sometimes it is limited to the reflections of the pleura separating the 
lobes of the lung. 

A 




B 



Fig. 257. — Transverse section of lung from a ease of pleuropneumonia, showing great thick- 
ening of the pleura (A) and consolidation of one of the lobes of the lung (B). 

Microscopically, the exudate consists of fibrils or flakes or granular 
masses of fibrin more or less infiltrated with round cells. Beneath this 
the endothelium of the pleura is found to be somewhat thickened by 
proliferation and some of the cells are detached. Two conflicting views 
have been entertained regarding the origin of fibrin formation in the 



DISEASES OF THE RESPIRATORY SYSTEM 



589 



pleura. According to one, the deposit is purely exudative and the endo- 
thelium is in nowise involved, being found intact under the fibrinous 
layer. According to the other view the fibrin formation is partly de- 
pendent upon destruction of endothelial cells. Whichever explanation 
is correct, there almost always remains a broken layer of endothelial 
cells in the acute and subacute stages. This may be removed when ad- 
hesions and chronic thickening obliterate the membrane. The con- 
nective tissue beneath the endothelium and the subpleural connective 
tissue are infiltrated with round cells and the blood-vessels are hyper- 
emic. In favorable cases and when the process has been slight a gradual 
reabsorption of the exudate takes place, and the integrity of the pleura 
may be restored completely. When the exudate has been more exten- 
sive and the agglutination of the pleural surfaces has been considerable, 
new blood-vessels from the capillaries of the pleura penetrate the 
fibrinous exudate, fibroblastic cells develop from the older connective- 
tissue cells, and gradually organization takes place, so that the adjacent 
layers of pleura are bound together by connective tissue, the fibrinous 
exudate gradually undergoing absorption and disappearing. The ad- 
hesions thus formed are at first delicate and quite cellular, but are later 
converted into dense, sclerotic bands. When fibrinous pleurisy occurs 
repeatedly, as in tuberculosis of the lungs, and is not sufficiently ex- 
tensive to cause adhesions, the surface of the pleura may become thick- 
ened and opaque in spots from proliferation of the connective tissue. 
In this way considerable chronic thickening of the pleura may ensue. 

Serofibrinous pleuritis may be simply a further stage of the fore- 
going form, though in many instances it begins almost at once as a 
serous exudation into the pleural sac. The liquid is heavier than 
dropsical fluid and contains flakes and shreds of fibrin. Microscopic- 
ally, it is found to contain white and red blood-corpuscles in small 
numbers, and occasionally detached endothelial cells. Sometimes the 
number of red corpuscles increases considerably, and there may be a 
gradual transition to the hemorrhagic form of pleuritis. The amount 
of liquid varies from a few cubic centimeters to several liters; and the 
pleura itself shows a more or less extensive coating of fibrinous exudate. 
The lung is pressed backward, as in pneumothorax or hydrothorax, and 
the adjacent organs (heart, liver) are displaced. 

Purulent pleuritis, empyema, or pyothorax, is always the result of mi- 
cro-organismal infection. The process may begin as a purulent pleuritis, 
or as a primary serofibrinous pleurisy, secondary pyogenic infection 
occurring either from within the body or through infected aspirating 
instruments from without the body. It may supervene upon pneu- 
monia, tuberculosis, or abscesses in adjacent parts (subdiaphragmatic). 
When a transition of the latter kind occurs the exudate is seen to be- 
come more and more turbid; the number of pus-corpuscles gradually 
increases until the liquid is quite purulent. Spontaneous discharge of 
empyema may occur and most frequently takes place through the 
lung and bronchi. More rarely rupture occurs through the chest walls 
anteriorly between the ribs. When rupture has occurred through the 



590 



A TEXT-BOOK OF PATHOLOGY 



lung and bronchi the fistulous communication may remain open and 
pneumothorax may ensue. 

The pleura in empyema shows more or less abundant granulations, 
which in case of discharge of the liquid serve eventually to unite the 
costal and pulmonary pleura by firm fibrous adhesions. Occasionally 
the pus may be completely absorbed, or it may undergo gradual inspissa- 
tion, remaining as a more or less cheesy detritus, which may finally 
become calcareous. Such terminations, however, are rare. Again, the 
adhesions may surround an area of much compressed lung and enclose 
the exudate over this area. Thus, we have encapsulated pleurisy. 
In the healing of empyema, retracting scars are common, with the result 
that the lungs, chest wall, or both are distorted. 

Hemorrhagic pleuritis is generally the result of tuberculous infec- 
tion or of malignant disease of the lungs and pleura. Pleuritis may 
also take a hemorrhagic form in old and cachectic individuals, or in 
persons suffering from scurvy, purpura, and similar diseases. As a 
rule, the liquid is serous, with considerable admixture of blood, but in 
tuberculous and malignant pleuritis it is sometimes well nigh pure 
blood. 

Chronic Pleural Thickening. — This term is used to include cases of 
thickening of the pleural membrane following various forms of acute pleu- 
risy, and also cases of a progressive productive character. To the latter 
alone the term chronic pleurisy is, strictly speaking, applicable. In either 
case the pleura is thickened by fibrous overgrowth, sometimes uniformly, 
at other times in the form of localized thickenings or adhesions. The 
subpleural pulmonary tissue may become implicated. Eventually, the 
thickened pleura contracts, and if adherent to the chest wall may cause 
retractions. The pulmonary tissue is compressed and the bronchi not 
rarely become distorted. In either primary or secondary chronic pleu- 
ritis there may be a total obliteration of the pleural cavity. The pleura 
becomes thick, opaque, and is poorly supplied with blood-vessels. Car- 
tilaginous or calcareous change may occur. 

Associated Lesions in Other Parts. — Though pleuritis is frequently 
the result of acute or chronic affections of the lung, it often occasions 
secondary disorders in the latter organ. The subpleural lymphatics 
are commonly distended with cells, and the inflammatory process may 
extend for considerable distances along these channels into the inter- 
lobular septa of the lung. In empyema the resulting purulent lymph- 
angitis and perilymphangitis lead to striking pathological appearances 
(see Pneumonia). The lung also suffers from direct pressure in serous 
and purulent pleuritis. If the compression to which it is subjected is not 
relieved by absorption of the liquid or by its removal by aspiration, the 
alveolar epithelium degenerates and proliferative inflammation takes 
place in the connective tissue, so that a permanent contraction of the 
lung results. The removal of the liquid at this stage is not followed by 
the return of the lung to its proper size and function. On the contrary, 
the removal or absorption of the liquid in these cases, especially when 
they occur in young children, causes a sinking in of the ribs and curvature 



DISEASES OF THE RESPIRATORY SYSTEM 



591 



of the spinal column, and the heart and other adjacent organs may be 
permanently displaced. Most remarkable deformities of the chest may 
occur. Less extensive contraction of one side of the chest, or displace- 
ment of the heart, may result from the contraction of bands of adhe- 
sions, without marked collapse of the lung. 

Pathological Physiology. — Acute pleurisy occasions marked local 
symptoms, beginning with sharp pain on the side affected. This is 
usually due to the local inflammation and rubbing of the affected parts. 
There may, however, be extensive neuralgic pains radiating from the 
center of infection. With the development of effusion, the pain, as a 
rule, subsides, as does also the irritative cough which attends the first 
stage, but shortness of breath develops in correspondence with the 
amount of effusion. Very extensive effusion in the chest may, however, 
cause even more marked pain and tenderness than dry pleural inflam- 
mation. The infection in simple pleurisy seems to be a mild one, as 
fever and constitutional symptoms are rarely marked. Sometimes the 
temperature is a fluctuating one, and sweating and constitutional de- 
pression further suggest suppuration, though the effusion is purely 
serous. Irregular fever and constitutional symptoms of the kind indi- 
cated are habitual in empyema. 

INFECTIOUS DISEASES 

Tuberculosis of the pleura, or tuberculous pleuritis, may be either 
primary or secondary. Cases of the former are comparatively rare. 
In most instances the pleural disease is secondary to tuberculosis of the 
lungs or to tuberculosis of other adjoining parts. Hematogenic infec- 
tion may occur under the same conditions as hematogenic infection of 
the lungs, and frequently the lungs and pleura? are studded with miliary 
tubercles at the same time. 

When the pleural disease is secondary to tuberculosis of the lungs 
the appearances vary considerably. In many cases small gray or yellow 
tubercles are found in the subpleural connective tissue and in the pleura, 
and the surface may be coated with fibrinous exudate, while the cavity 
of the pleura may be more or less distended with serofibrinous, hemor- 
rhagic, or purulent liquid. Not rarely the liquid effusions are reab- 
sorbed and dense adhesions are formed, or great thickening of the 
pleura results. Sometimes considerable calcification of the thickened 
pleura and of the inspissated exudate is the terminal result. The tubercle 
bacilli are often difficult to demonstrate in the liquid, even by injec- 
tions into animals, though they may be present in the pleura itself. 

Syphilis of the pleura is a doubtful condition. Fresh pleuritis may 
be found in the neighborhood of a syphilitic gumma ; and there are cases 
of considerable pleural thickening in syphilitic persons in which the 
disease may possibly be syphilitic, though in these cases, as in similar 
indurative conditions in the lungs, there is considerable doubt as to the 
essential nature of the disease. 



592 



A TEXT-BOOK OF PATHOLOGY 



TUMORS AND PARASITES 

Tumors of the pleura are comparatively rare. Fibromata and 
lipomata are occasionally seen as small nodular masses in the serous or 
subserous coat of the costal or visceral pleura. Chondromata and even 
osteomata have been observed. More frequently calcification and ossi- 
fication of portions of the thickened pleura take place after pleuritis. 

Primary sarcoma may spring from the subpleural connective tissue, 
and, according to Coats, is especially common in children, and is most 
frequently of the spindle-cell variety. Primary endothelioma of the pleura 
(Fig. 258) has been studied by a number of investigators. In a case under 
the observation of one of us it presented itself as a more or less uniform 




Fig. 258. — Endothelioma of pleura. 



thickening of the pleura of one side, involving the diaphragmatic re- 
flection in particular. The cavity was filled with hemorrhagic fluid and 
there were some nodular enlargements on the surface (Figs. 259 and 260). 
This is the usual appearance presented. Metastasis may occur in the 
lung beneath the diseased pleura, or even in more distant parts. There 
is a tendency for pleural endothelioma to be accompanied by fibrosis, 
and oftentimes adhesions are seen. 

Secondary tumors of the pleura may occur by metastasis or by 
direct extension. In the former manner sarcomata and carcinomata 
sometimes involve this structure; by the latter method of involvement 
mammary tumors and new growths of the mediastinum, the ribs, or 
other adjacent structures may extend to the pleura. 



DISEASES OF THE RESPIRATORY SYSTEM 593 

Parasites. — Echinococcus cysts may originate in the subserous con- 
nective tissue of the costal or the visceral pleura, and may rupture into 




Kg. 259. — Endothelioma of pleura: the pleural cavity was distended with effusion, and 
the lung was compressed and invaded by secondary nodules. 




Fig. 260.— Microscopical section from Fig. 259. 



the pleural cavity. Psorospermiae have been found in pleural effusions. 
The dysenteric ameba has been found in the pus of empyema following 
hepatic abscess. 

38 



CHAPTER V 



DISEASES OF THE GASTROINTESTINAL TRACT 
The Mouth 
congenital abnormalities 

The most frequent defects in the development of the mouth are 
cleft palate and harelip. In the former of these the entire hard palate 
may be divided, generally to one side of the middle line; and there may 
be associated harelip and fissure of the soft palate. Anteriorly, the 
division occurs between the superior maxillary bone and the inter- 
maxillary bone, the fissure of the lip being also to one side and often 
extending into the nostril. The soft palate is divided along the middle 
line, and the uvula may be separated into lateral halves. The lip may 
be cleft on both sides, so that there is a small central portion connected 
with the septum of the nose and separated from the lateral portions of 
the lip. Harelip is more frequently unassociated with cleft palate. 

Complete absence of the lips, or unusual shortness, especially of the 
upper lip, excessive largeness of the mouth by extension of the fissure 
outward toward the ear, and imperfect development of the lower jaw- 
bone, are rare congenital conditions. 

Macrocheilia (large lips), macroglossia (large tongue), and ankylo- 
glossia (tongue-tie) are congenital malformations. 

CIRCULATORY DISTURBANCES 

Anemia of the mucous membranes of the mouth is seen in cases of 
general anemia, and is often one of the most striking evidences of that 
condition. It is particularly noticeable in the lips. 

Hyperemia. — Active hyperemia occurs in the early period of various 
inflammations, or as a forerunner of some infectious diseases not local- 
ized to the mouth; while passive hyperemia is met with as the result of 
obstruction of the circulation in pulmonary and cardiac diseases. 

Hemorrhages in the form of small petechia? occur in purpura and 
other hemorrhagic diseases, and sometimes in infectious fevers. 

INFLAMMATION 

Inflammation of the mucous membrane of the mouth is termed 
stomatitis; inflammation of the tongue is designated by the name 
glossitis. 

Stomatitis may be of varying character and intensity. 

594 



DISEASES OF THE GASTROINTESTINAL TRACT 



595 



Catarrhal stomatitis may result from direct irritation by hot liquids 
or chemical substances, or may occur in depressed conditions of the 
general system, possibly as a consequence of infection. It is more com- 
mon in children than in adults. The mucous membrane of the mouth 
is red and usually covered with considerable liquid exudation. When 
the inflammation is intense, small vesicular cysts may form from dis- 
tention of the mucous glands, and even localized erosions may appear. 
When the inflammation has continued for a long time, or has been re- 
peated, there may form upon the surface silvery-white, slightly elevated 
spots, which result from a hyperplasia of the epithelium, a form of kera- 
tosis. This condition has been designated by the name of leukoplakia. 

Mild catarrhal conditions of the mucous membrane of the mouth 
are especially common on the tongue, the epithelium of which con- 
stantly desquamates. In the course of gastro-intestinal and other dis- 
eases the desquamation may be more active, the cells, however, being 
retained upon the surface. Portions of food and bacteria cling to the 
masses of desquamated cells, and in this manner the whitish or brownish 
furring of the tongue so commonly met with in various diseases is formed. 
Sometimes the heaping of epithelial cells takes place in localized areas, 
and extends in peculiarly irregular patches, which, from their resem- 
blance to maps, have given rise to the term "geographical tongue." 
In chronic cases the whitish spots of leukoplakia alluded to above are 
formed. 

Aphthous stomatitis occurs in children under conditions of mal- 
hygiene and debility, or as a result of gastro-intestinal and other dis- 
eases. Local irritation often plays an important part. There appear 
in the mucous membrane, especially of the lower lip and gums, small 
whitish spots lying upon an inflamed base. Usually these are separated, 
but sometimes confluence occurs, though there is rarely extensive 
spreading. The whitish membrane covering or constituting the spots 
is composed of degenerated epithelium, and sometimes of fibrin, so that 
the term "croupous stomatitis" may in some cases be applied. The 
lesions are superficial and rarely lead to actual ulceration. It has been 
held that the preliminary lesion is a vesicle; this, however, does not 
appear to be frequent, and is certainly not essential. 

Foot-and-mouth Disease. — A similar affection occurs in animals, 
particularly in cows, sheep and goats, and is designated foot-and-mouth 
disease. This condition is contagious, and considerable epidemics 
have occurred among persons drinking the milk of infected animals. 
The specific cause is unknown ; the virus is ultramicroscopical and filter- 
able. The process is one of hyperemia and thickening of the corium 
with vesicle formation in the epithelium. These may rupture and form 
shallow ulcers. 

Bednar's aphthae are small ulcers found in the mouths of sucking 
infants and situated at the lateral portions of the palate over the ends 
of the pterygoid processes, on other parts of the hard palate, or occa- 
sionally on the soft palate. They are probably caused by traumatism 
occurring in the act of sucking. 



596 



A TEXT-BOOK OF PATHOLOGY 



Ulcerative stomatitis may be met with in various parts of the mouth, 
especially in the gums. In young children it is frequently the result 
of malnutrition and lack of cleanliness of the mouth. Various sapro- 
phytic micro-organisms normally found in the mouth may, under suit- 
able conditions, aid in the production of ulcerative stomatitis. Among 
these the Leptothrix buecalis, Indococcw vaginatus, Bacillus maximus 
buccalis, Spirillum sputigenum, and Spirochceta dentium have been iso- 
lated. Pyogenic cocci may also play a part in its etiology. In various 
cachectic diseases, particularly in scurvy, the gums become soft and 
spongy and tend to ulcerate. Mercurial and other forms of poisoning 
may lead to extensive ulcerations. Deeper ulcerations are found upon 
the sides of the tongue or the inner part of the lip in cases of injury due 
to the sharp edges of broken or carious teeth. Ulcerative stomatitis 
may be secondary to necrotic conditions of the bones or suppurative 
inflammations about the roots of teeth. Ulceration beneath the tongue 
is met with in many cases of whooping-cough, and is due to the irritation 
of the teeth in the paroxysms of coughing. 

In ordinary cases of ulcerative stomatitis the gums at the junction 
with the teeth become reddened and soft, and may present hemorrhagic 
infiltration. Later, the epithelium of the surface is destroyed and open 
ulcers result. Considerable suppuration may occur, and the teeth 
may be loosened and dislodged. 

A form of disease about the necks of the teeth and secondarily 
involving the gums has been termed pyorrhea alveolaris. The process 
is one of cementitis and pericementitis with a separation of the cemen- 
tum from the lining of the alveolar socket. The cementum is thus de- 
prived of its nourishment normally supplied by this peridental mem- 
brane. The discharge of pus from the gums surrounding the teeth gives 
the disease its name. It has been ascribed to infection with spirochetes, 
anaerobes, and amebse, especially the Endamoeba buccalis. The impor- 
tance of the last is strengthened by the fact that pyorrhea is improved 
by the use of emetin. This condition has been viewed by some as a 
focal infection from which, as a source, bacteria and their products are 
swallowed or transferred by the blood to other organs, and there set up 
intoxications or infections. Thus, arthritis deformans, chronic adenop- 
athy, and aspiration pneumonia are supposed to arise sometimes. 

The method of origin of pyorrhea alveolaris is probably that tartar 
collects upon the teeth down to the gingival margin, below which food 
particles collect and infection occurs. This process, having at best a 
very limited outlet, turns to a purulent inflammation, leading to gingivi- 
tis and retraction of the gums. 

Pseudomembranous stomatitis is most frequently due to the action 
of the bacillus of diphtheria, and is, therefore, strictly speaking, diph- 
theria of the mouth. It is usually secondary to pharyngeal diphtheria, 
but may occur primarily upon the lips or other parts of the mouth. In 
some cases of aphthous stomatitis the lesion is, in reality, a pseudo- 
membranous one. 

Phlegmonous stomatitis is more common in the lips than in other 



DISEASES OF THE GASTROINTESTINAL TRACT 



597 



parts of the mouth, and may be the result of traumatic injuries with 
intense infection, or a secondary condition after facial erysipelas or 
other cellular inflammations of the face. The lips and cheeks may be 
greatly swollen, and suppuration may occur, forming abscesses which 
tend to rupture into the mouth. A chronic form of inflammation of the 
deeper tissues of the lips may lead to hypertrophy. This is especially 
common in the upper lip as the result of long-standing coryza or 
eczema. 

Gangrenous stomatitis, or noma, affects the mucous membrane 
of the cheeks, and occurs in ill-nourished children, especially after 
measles and other infectious fevers. There is formed a sloughing ulcer 
on the inner side of the cheek, and inflammatory induration involving 




Fig. 261. — Case of noma (Children's Hospital). 



the entire thickness of the cheek. The skin at first presents a dark-red 
or bluish discoloration, and later extensive destruction (gangrene) may 
occur (Fig. 261). The pathological changes are those of a rapid necrosis 
of all the tissues, and micro-organisms of suppuration and sapro- 
phytes are usually present. Pseudodiphtheria bacilli have been found 
in some cases. Various spirochetes have been observed. The most 
common finding is a micro-organism belonging to the necrosis bacilli, 
but its pathological importance is not established. Putrefactive 
changes cause a fetid odor. Intense septic infection and intoxication 
generally attend. 

Milder forms of gangrenous stomatitis affecting the gums around 
carious teeth are occasionally observed. 



598 



A TEXT-BOOK OF PATHOLOGY 



Associated Conditions in Stomatitis. — In many cases the inflam- 
mation may extend from the mucous membrane of the mouth poste- 
riorly to the pharynx. Very commonly the lymphatic glands of the 
neighborhood are involved, with enlargement of the submaxillary or 
even the cervical glands. In some cases, especially in mercurial stoma- 
titis, the salivary glands are coincidently or consecutively swollen and 
inflamed. Increased flow of saliva (ptyalism or sialorrhea) is a fre- 
quent symptom. In intense cases, especially in gangrenous stomatitis, 
parenchymatous degenerations of other organs may result from general 
toxemia. 

Glossitis. — Superficial catarrhal inflammations have been referred to. 
The tongue may be involved in the various forms of stomatitis and shows 
similar changes. More extensive inflammations of the tongue, leading 
to 'parenchymatous glossitis, may result from injuries, especially when 
accompanied by infection. The entire organ may in these cases be 
swollen, and there is round-cell infiltration with a tendency to suppura- 
tion. Localized parenchymatous glossitis with ulceration may occur 
from injury by carious teeth. 

Hemilateral glossitis, sometimes attended with the formation of 
herpetic vesicles, is occasionally observed, and is probably dependent 
upon disease of the chorda tympani nerve. 

ATROPHY AND DEGENERATIONS 

Atrophy of the muscles of the tongue and cheeks may occur in 
association with nervous diseases (bulbar palsy) . Physiological atrophy 
of the gums follows loss of the teeth in old age. 

Degenerations of the mucous membrane usually accompany in- 
flammations. 

Under the name of nigrities, or black tongue, is described a form of 
hypertrophy of the papillae of the tongue with pigmentation. The 
dorsum of the tongue may be covered with a hair-like coating of dark- 
brown or blackish color. The cause of this affection is obscure. 

INFECTIOUS DISEASES 

Thrush, or parasitic stomatitis, is met with in young children, 
and is due to the action of a micro-organism known as O'idium albi- 
cans. There are formed upon the mucous membrane white patches 
resembling curdled milk, and varying in size from mere points to large 
areas. These tend to coalesce and to spread. The mucous membrane 
is reddish and inflamed. The back and sides of the tongue and the inner 
parts of the cheeks are favorite seats. Microscopically, the white coating 
is composed largely of mycelial threads of the parasite, with which are 
mingled degenerated epithelial cells and generally also other micro- 
organisms, notably micrococci. The process may extend to the pharynx, 
and sometimes as far as the bronchi or the stomach, through the larynx 
and esophagus. 



DISEASES OF THE GASTROINTESTINAL TRACT 



599 



Tuberculosis of the mouth may be primary or secondary. The 
latter is especially frequent at the root of the tongue, and is secondary 
to tuberculosis of the larynx or pharynx 
(Fig. 262). Small nodular masses of 
tubercles are formed, and tend to undergo 
cheesy degeneration, forming ulcerated 
areas. Primary tuberculosis leading to 
ulceration may occur upon the lips or 
upon the tongue as a result of direct in- 
oculation, as in the kissing of a tubercu- 
lous person. Nodular masses are formed, 
which at first present themselves as papil- 
lary elevations, but subsequently undergo 
characteristic necrosis. Tuberculous ul- 
cers are usually irregular or undermined, 
and the bases are more or less caseous 
and infiltrated by tubercles. The injury 
of the tongue by the teeth, and the favorable soil offered for the re- 
tention and multiplication of the micro-organisms in carious teeth, may 
play a part in the causation. 




Fig. 263. — Actinomycosis of the cheek (Illich). 



Lupus of the face may extend to the mouth. It is distinguished by 
the associated cicatrization. Secondary carcinomatous change may 
occur in the base of the lesion (lupus carcinoma). 

Syphilis is most frequently secondary, occurring in the form of 




600 



A TEXT-BOOK OF PATHOLOGY 



mucous patches upon the lips or tongue, or as more elevated condylo- 
mata, which in healing cause irregular contractions or whitish or opaline 
thickenings of the mucous membrane. A simple syphilitic catarrhal 
angina may occur. Gummatous infiltrations may appear in a localized 
form or as irregular involvements. On the dorsum of the tongue, their 
commonest seat in this organ, they produce deep, ragged excavations. 
They are usually deep seated and, on healing, fissuration and deformity 
may result. The tongue is the most frequent seat. The primary 
syphilitic lesion (chancre) resulting from direct inoculation is occa- 
sionally observed upon the lips, tongue, or pharynx. 

Actinomycosis affects the tongue, gums, and jaw-bone, and is char- 
acterized by a slowly infiltrating process with a tendency to necrosis 
and suppuration, in which the alveolar processes of the jaw-bone are 
generally attacked. The lesion in the mouth may be insignificant, 
while the secondary involvement of the cheeks or of the lymphatic 
glands below the jaw and in the neck may be extensive (Fig. 263). 

Leukemic Stomatitis. — In acute leukemia ulcers of the mouth 
are frequent at the onset and throughout the disease. The gums may 
present an ulcerated appearance resembling that seen in scurvy. Con- 
siderable necrosis and hemorrhagic infiltration are common. Xodular 
infiltration of the adenoid tissues at the base of the tongue and in the 
pharynx also occur in acute leukemia, but more commonly in the 
chronic form. 

TUMORS 

Papillomatous growths of the mucous membrane are occasionally 
observed. Fibroma, lipoma, myxoma, and even chondroma are rare 
forms of tumors of the submucous tissue of the tongue or other parts 
of the mouth. Not rarely they are congenital. Lymphadenoma or 
lymphosarcoma may occur at the root of the tongue, where it takes origin 
from the lymphatic follicles or the lingual tonsil. Sarcoma of other 
parts of the mouth is rare, excepting as an extension from sarcoma of the 
jaw-bone and other parts. 

Epithelioma or carcinoma is the most important new growth of the 
mouth, and in nearly all cases is of the squamous-celled variety. The 
favorite seats' are the lower lip, usually toward one side of the mouth, 
and the tongue. It appears as an irregular nodular elevation which 
tends to ulcerate upon the surface and spread to adjacent structures. 
Metastasis usually occurs to the submaxillary and cervical lymphatic 
glands. 

The name "epulis" is a clinical term applied to tumors arising from 
the alveolar process. Sarcoma and endothelioma are the commonest 
forms. 

Nodular masses having the structure of the normal thyroid gland 
have been found at the base of the tongue. 

Cystic formations, due to agglutination of the mouths of the mucous 
glands, are met with upon the tongue and lips. 

Cysts are especially frequent beneath the tongue, at the sides of the 



DISEASES OF THE GASTROINTESTINAL TRACT 



601 



frenum. These have been termed ramda, and are formed by the dilata- 
tion of the ducts of the small mucous glands. At times ranula may be 
a cystic dilatation of a duct of the sublingual salivary gland or that of a 
submaxillary gland. Ranula is usually found as a rounded or elliptical 
tumor which may fill the floor of the mouth and displace the tongue 
backward and upward. The contents consist of somewhat gelatinous 
albuminous liquid. They may be due to stenosis of the excretory duct 
by inflammation or blocking by a stone. Cysts may arise at the base 
of the tongue from the remains of the thyroglossal duct. 

Hemangioma, both of the teleangiectatic and cavernous varieties, is 
occasionally seen, but a more important tumor is lymphangioma, affecting 
the tongue and lips and giving rise to the conditions known as macro- 
glossia and macrocheilia. In these conditions there is a uniform enlarge- 
ment of the tongue or lips, and on section distended lymphatic spaces 
more or less filled with liquid and round cells are detected. Such en- 
largements are usually congenital, and are especially met with in 
cretins. 

Angiomata of sarcomatous or carcinomatous nature have been seen 
in the tongue. 

The Teeth 

Anomalous Development. — Unnatural largeness or, on the con- 
trary, lack of development is frequently observed. Complete absence 
of the teeth has been noted. Numerical increase or decrease is fre- 
quent. Delay in the eruption of the teeth and irregularity in their for- 
mation occur in rachitis; and a form of maldevelopment of the upper 
central incisor teeth of the permanent set is observed in cases of con- 
genital syphilis ( Hutchinson's teeth) . The characteristics of this condi- 
tion are the wedge shape of the teeth, the cutting-edge being smaller 
than the crown, and the concave notching of the cutting-edge (see Fig. 
119). Hutchinson's teeth are not entirely peculiar to congenital syph- 
ilis, being sometimes seen in rachitis. 

Caries of the teeth results from malnutrition, digestive disturbances, 
and lack of cleanliness. Micro-organisms which lead to acid fermenta- 
tion contribute to the causation by forming acids which dissolve calcium 
salts, soften the enamel, and occasion fissures through which other 
bacteria (bacilli and micrococci) may gain entrance into the channels of 
the dentin. The soft teeth of pregnant women are due to the reduction 
of calcium which is being given to the fetus. 

The carious process consists in a gradual disintegration of the 
enamel and dentin, with the formation of more or less granular detritus 
in which bacteria are abundant. The process may penetrate to the 
pulp of the teeth and set up a secondary inflammation, or pulpitis. 

Inflammation of the pulp of the teeth may occur in association 
with caries, or sometimes independently. The pulp becomes reddened 
and swollen, and may present hemorrhages and, later, suppuration. 
The inflammatory process tends to spread through the roots of the 
teeth to the tissues surrounding the roots and to the alveolar perios- 



602 



A TEXT-BOOK OF PATHOLOGY 



teum. Abscesses may thus be formed about the teeth, and may spread 
to the tissue of the gums (alveolar abscesses), eventually rupturing upon 
the surface. 

Tumors composed of tissue resembling the normal dentin are spoken 
of as odontomata, and may be solid or cystic. They arise from the pulp 
during the process of development and form irregular outgrowths of the 
crown or roots. Similar outgrowths, resembling the enamel or dentin, 
or cement substance, are more frequent in later life, and have been desig- 
nated as odontinoids. 

Sarcomata and fibromata may spring from the pulp during the de- 
velopment of teeth or from the connective tissue about the roots; and 
polypoid outgrowths (hypertrophied granulations) from the pulp may 
be met with in association with caries of the teeth and pulpitis. 

The most important tumor is the giant-celled sarcoma of the alveolar 
process of the jaw. This is known by the name of "epulis," though, 
strictly speaking, the term is applied rather to the situation than to the 
kind of tumor. Extensive enlargements of the jaw-bone and destruction 
of the surrounding tissues may ensue. 

Cysts are met with in the alveolar processes, and arise from the 
primary follicles in which the teeth are developed. These may contain 
epithelium and teeth. There are also cystic tumors of the teeth-sockets 
from the periosteum of the jaw-bone. 

The Pharynx and Tonsils 
circulatory disturbances 

Anemia of the soft palate and other portions of the pharynx occurs 
in general anemia and in cases of phthisis or other wasting diseases. 
The mucous membrane may be decidedly pallid. 

Active hyperemia or congestion occurs in the beginning states of 
inflammation and when irritants have been in direct contact with the 
mucous membranes. 

Passive hyperemia is seen in heart disease, emphysema, phthisis, 
and other chronic pulmonary affections. In these cases the mucous 
membrane is dark red, and not rarely becomes somewhat edematous. 

Edema of the pharyngeal tissues is found in association with in- 
flammatory affections, and may occasion considerable stenosis. 

Hemorrhages may be the result of direct injury, as in the swallowing 
of fish-bones and the like, or may occur in* the form of petechia? in pur- 
pura and other hemorrhagic diseases and in intense infections (small-pox, 
septicemia). 

INFLAMMATIONS 

Catarrhal pharyngitis, or angina, may affect the entire lining mem- 
brane of the pharynx, or may be limited to the tonsils or other parts. 
It results from direct irritation by hot liquids or chemical substances, 
from exposure to cold, and particularly from infections. Angina, or 



DISEASES OF THE GASTROINTESTINAL TRACT 



603 



sore throat, is met with in many of the infectious fevers, or may appear 
as an independent infection. 

The mucous membrane presents a bright-red color, is somewhat 
swollen, and covered with tenacious exudation composed of mucus and 
desquamated cells. Small vesicular elevations may form, and after the 
rupture of these, erosions or even superficial ulcers are sometimes seen. 
Occasionally there are hemorrhagic extravasations. 

A form of catarrhal pharyngitis, known as herpetic angina, is analo- 
gous to herpes of the skin, and may accompany facial or labial herpes. 

Chronic catarrhal pharyngitis is met with in persons who use the 
voice excessively, especially in the open air. It may also result from the 
abuse of tobacco or alcohol. The posterior wall of the pharynx and the 
pillars of the soft palate are particularly involved. The mucous mem- 
brane is swollen in the earlier stages, but later becomes atrophic, and is 
marked by slight granular elevations, which are either hyperplastic 
lymph-follicles or distended mucous glands. The veins in the sub- 
mucous tissue are enlarged, and are visible through the atrophic mucous 
membrane as tortuous channels. Chronic hyperplasia of the tonsils 
and chronic laryngitis are frequently associated. 

Phlegmonous pharyngitis may result from wounds of the pharynx, 
or may be associated with intense infections, such as pseudomem- 
branous tonsillitis and pharyngitis, particularly the forms due to 
streptococci. It may result from pustular pharyngitis in small-pox, or 
from glanders of the pharynx. Phlegmonous tonsillitis sometimes ex- 
tends to the peritonsillar tissues as far as the retropharyngeal wall. 

The soft palate, uvula, arches, or other parts affected are swollen 
and tensely distended. There may be congestion or deep cyanosis and 
edematous exudation. The usual termination is suppuration, but 
sometimes gangrenous necrosis ensues. General septicemia is fre- 
quently the result. 

Retropharyngeal Abscess. — This condition may occur secondarily 
after traumatic or infectious pharyngitis as above described. Phleg- 
monous pharyngitis primarily affecting the retropharyngeal tissues may 
be due to caries of the cervical vertebra?; occasionally it occurs in the 
infectious fevers in consequence of embolism, or infection of the deep- 
seated lymphoid nodes of the pharynx. 

Pseudomembranous pharyngitis may be caused by the Mycobac- 
terium diphtheria^, in which case the disease is diphtheria, or it may be 
due to a variety of other micro-organisms, or to irritating gases, steam, 
and like causes. Non-diphtheritic pseudomembranous pharyngitis is 
especially common as a complication of scarlatina, measles, and other 
infectious diseases, and seems in these cases to be caused by the Strepto- 
coccus pyogenes. The appearance of the throat may be identical with 
that observed in diphtheria, but extensive necrosis is more common, 
while typical pseudomembranes are less frequent. 

The mucous membrane and the underlying parts, especially the 
tonsils, become greatly swollen and edematous, and subsequently suffer 
necrotic changes. 



604 A TEXT-BOOK OF PATHOLOGY 

There is formed upon the surface of the throat a whitish or yellowish 
patch, or several patches, which tend to coalesce and extend from the 
region of the tonsils to the pillars of the fauces and the uvula, or to the 
mouth, nose, or larynx. The pseudomembrane is quite firmly attached 
to the mucous membrane, and cannot be removed without tearing away 
part of the underlying tissues. Microscopically, the deposit is found to 
consist of granular or fibrillar fibrin entangling more or less degenerated 
leukocytes and epithelial cells. In the deeper layers intense congestion 
and round-cell infiltration are observed; in the superficial strata de- 
generated cells and detritus, together with masses of bacteria, are 
conspicuous. 

The neighboring lymphatic glands, notably those below the angle 
of the jaw, enlarge and may suppurate, and sometimes extensive cellu- 
litis and suppuration of the floor of the mouth (Ludwig's angina) occur. 
There are intense systemic intoxication and infection, and secondary 
lesions are frequently developed in various organs (nephritis, myocardi- 
tis, etc.). The non-diphtheritic forms of pseudomembranous pharyn- 
gitis may be distinguished from the diphtheritic forms, in typical cases, 
by the greater intensity of the local (necrotic) processes, the earlier and 
more marked involvement of the local lymphatic glands, and by the 
greater tendency to nephritis ; but, unfortunately, atypical cases are very 
common, and an absolute diagnosis can be made by bacteriological 
study alone. 

Tonsillitis may be a part of a general pharyngitis, or it may occur 
as an independent affection. Several varieties are described. 

Catarrhal tonsillitis results from the same causes as catarrhal phar- 
yngitis in general, and presents similar appearances. The tonsils are 
usually somewhat enlarged. 

Lacunar or follicular tonsillitis occurs from similar causes, and 
may involve the normal tonsil or one affected by chronic hypertrophy. 

The surface of the tonsil is marked with small 
white or yellowish spots, into which the end 
of a probe may be inserted. These are the 
lacunae or crypts distended with masses of 
epithelial cells more or less degenerated. 
Bacteria of various kinds may be found in 
the contents of the lacuna?, and doubtless 
play an important part in the etiology. 
Staphylococci, streptococci, pneumococci, tu- 
bercle bacilli, and the bacillus of diphtheria 
have all been observed. The latter two 
forms may be present merely as accidental 
associations, but may possibly play an eti- 
ological part. Ulceration may occur in the 
walls of the lacunae, and the surface of the tonsil may be con- 
siderably broken down. In other cases the bacteria may penetrate 
the tonsil at the bottom of the lacunae, and phlegmonous tonsillitis, 
or quinsy, may result (see below). The contents of the lacunae may be 




A B 
Fig. 264. — Crypts in cases 
of tonsillitis: A, Acute lacu- 
nar; B, chronic hypertrophic: 
o, surface epithelium; b, ac- 
cumulated contents of crypt; 
c, lymphoid follicles surround- 
ing crypt (Kaufmann). 



DISEASES OF THE GASTROINTESTINAL TRACT 



605 



discharged upon the surface, and may adhere for a time as a yellowish- 
white caseous pellicle, resembling diphtheritic pseudomembranes in 
appearance. In other cases the contents of the crypts are retained, 
undergo inspissation, and may even calcify. A certain amount of 
catarrhal pharyngitis may be associated, but the follicular ulcers are 
rarely seen beyond the tonsils. 

Phlegmonous tonsillitis, abscess of the tonsil, or quinsy, may be 
the result of simple catarrhal or of follicular tonsillitis, or may be asso- 
ciated with phlegmonous inflammation of other parts of the pharynx. 
One or both of the tonsils may be affected. Redness and swelling are 
noted in the earlier stages, but later the mucous membrane is pallid 
or even yellowish. Microscopically, diffuse round-cell infiltration and 
eventually focal collections leading to abscess formation are detected. 
The peritonsillar tissues may be involved, and spreading phlegmonous 
inflammation results. Rupture may take place into the pharynx, or the 
ulceration may extend outward, causing discharge upon the neck at the 
angle of the jaw. The internal carotid artery may be perforated. 

Enlargement of the submaxillary and cervical lymphatic glands 
is commonly observed. General septicemia of mild type is not infre- 
quent; myocarditis, endocarditis, and nephritis may result. The asso- 
ciation of tonsillitis and rheumatism has occasioned much discussion. 
It is very probable that rheumatism frequently follows tonsillitis, 
the latter being the first effect of micro-organismal invasion, which 
eventually causes rheumatism. 

Chronic tonsillar hypertrophy may result from repeated attacks of 
simple catarrhal or of follicular tonsillitis. The lymphatic constitution 
or status lymphaticus is a factor of importance. The tonsils are en- 
larged, usually irregularly so, and are harder than normal. On section 
the connective-tissue reticulum and septa are found increased, and the 
lymphoid follicles are likewise hyperplastic. Pressure upon the orifices 
of the lacunae not rarely causes obstruction and repeated attacks of 
lacunar tonsillitis. Retention and calcification of the contents of the 
crypts are particularly common in the- lacunar tonsillitis of hypertrophic 
tonsils. Chronic hypertrophy of the tonsils very often occurs in rachitic 
or badly nourished children in association with hyperplasia of the 
lingual tonsil and nasopharyngeal adenoid tissues — the clinical adenoids. 
Distinct evidences of inflammation are wanting in such cases, and the 
condition seems rather a form of simple hyperplasia of the lymphoid 
structures. 

Pathological Physiology. — Acute tonsillitis may occasion only 
local symptoms, such as pain, difficulty in swallowing, etc., but in many 
cases there are general symptoms — fever, disturbances of appetite, etc. 
The latter vary in severity according to the particular infectious cause 
of the disease. 

A chronically enlarged tonsil probably always contains bacteria, 
and this may constitute a focal infection, whence bacteria may be 
liberated to cause damage elsewhere. The streptococci of the tonsils 
have been suspected of responsibility for chorea, arthritis deformans, and 



606 



A TEXT-BOOK OF PATHOLOGY 



other subacute infections. Chronically diseased tonsils have been found 
to contain a toxic substance, which when absorbed excites antibodies 
like a parenterally introduced protein, and acts as a protoplasm 
poison. The glands containing streptococci seem to contain most of 
this poison. This may aid in the production of the above diseases. 

PRESSURE NECROSIS 

This condition occurs upon the anterior and posterior walls of 
the pharynx, opposite the cricoid cartilage. It is met with in marantic 
persons occupying a dorsal decubitus, and is caused by the backward 
pressure of the cricoid cartilage against the opposite vertebra. The 
mucosa becomes necrotic, and more or less extensive ulcerations are 
formed. Complete perforation of the pharyngeal wall sometimes 
occurs. 

INFECTIOUS DISEASES 

Diphtheria of the pharynx usually begins in the mucous mem- 
brane covering the tonsils, and spreads to the pillars of the fauces, to 
the uvula, the posterior wall of the pharynx, the cheeks and tongue, the 
posterior nares, or to the larynx. It rarely invades the esophagus, but 
may sometimes extend along this structure as far as the stomach. 

The specific cause is the Myco- 
bacterium diphtheria (see Diph- 
theria, p. 285). The character- 
istic lesion is a pseudomembrane, 
which is formed on the surface 
and within the mucous mem- 
brane. This first appears as a 
grayish or yellowish-white pel- 
licle, more or less firmly attached 
to the mucosa; it spreads rapidly, 
and may cover the whole of the 
pharynx in a day or two. In 
other cases the disease progresses 
slowly or remains quite limited. 
The underlying tissues become 
swollen by inflammatory infiltra- 
tion (cellular and edematous), 
and swallowing and breathing 
may then be greatly obstructed. When the pseudomembrane is re- 
moved from the surface a raw and more or less necrotic base is ex- 
posed. Microscopically, the surface of the pseudomembrane is found 
to consist of a mass of debris, often containing micrococci and other 
bacteria, as well as the specific organisms, in great numbers. Some- 
what more deeply the membrane is composed of a fibrinous reticulum 
or masses of fibrin entangling degenerated epithelial cells and leuko- 
cytes. Still more deeply the tissues of the phaynx are found intensely 




Fig. 265. — Pseudomembranous inflamma- 
tion of the uvula: a, a, masses of micrococci; 
6, b, necrotic cells; c, c, round-cell infiltration; 
d, d, fibrin network (Ziegler). 



DISEASES OF THE GASTROINTESTINAL TRACT 



607 



congested and infiltrated with round cells (Fig. 265). In the late 
stages of the disease extensive necrosis of the mucosa and submucosa 
may occur. 

In some cases diphtheria may undoubtedly present the lesions of an 
ordinary lacunar tonsillitis, and the clinician may be unable to deter- 
mine the nature of the disease. 

Associated Conditions. — Some enlargement of the lymphatic glands 
at the angle of the jaw is usual, and exceptionally this may terminate 
in suppuration. Lesions of the internal organs, especially the heart and 
kidneys, are not infrequent, and disease of the peripheral nerves is a 
common sequel (see Diphtheria, p. 287). 

Vincent's angina is a mildly infectious disease characterized by 
superficial ulceration upon which a lightly adherent pseudomembrane 
lies. The process usually begins upon or near the tonsils and spreads 
slowly; it is a superficial ulceration of the epithelium, while in the 
corium there is a moderate round-cell infiltration. The fusiform bacilli, 
and the spirilla probably growing from them, are found in the mem- 
brane and on the base of the ulceration (see page 340). 

Pharyngomycosis Leptothricia. — This condition is met with 
on the tonsils, and less frequently the pillars of the fauces, uvula, and 
other parts of the pharynx. It occurs in persons of lowered vitality, 
and seems to be caused by the Leptothrix biiccalis, a form of bacterium 
very commonly met with in the collections around the necks of the 
teeth. The lesions present themselves as milky-white and somewhat 
chalk-like outgrowths arising from the tonsillar crypts and the mucous 
glands. These are often tightly adherent, but occasion very little 
inflammation of the surrounding tissues. Microscopically, the thread- 
like parasite is found in abundance. 

Tuberculosis may occur in the pharynx in the form of subepithelial 
tubercles, which break down and occasion more or less extensive ulcera- 
tions. 

Tuberculosis of the tonsils may be primary or secondary. In the 
former case infection probably occurs from the invasion of the crypts by 
tubercle bacilli; this condition is doubtless more common than has 
generally been supposed. Secondary tonsillar tuberculosis usually 
follows tuberculosis of the lungs or larynx. In either case there are 
formed in the tonsils small tubercles which rapidly increase in size, fuse, 
and subsequently undergo caseous change. Discharge of the caseous 
matter upon the mucous surface is not unusual, and occasions ulcer-like 
formations. Secondary infection of the cervical and submaxillary 
lymphatic glands is not infrequent. 

Syphilis may occur in the pharynx in the form of the primary 
lesion or chancre, as simple catarrhal angina, as mucous patches, or as 
gummata. The last are prone to undergo ulceration with secondary 
cicatrization. Extensive distortion of the pharyngeal structures may 
be the result of the scar formation. 

Glanders and lepra sometimes invade the pharynx. 

Typhoid ulcers are occasionally met with. 



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A TEXT-BOOK OF PATHOLOGY 



TUMORS 

Among the tumors of the pharynx, fibroma, lipoma, and papilloma 
are occasionally found on the soft palate, uvula, or tonsils. Of the 
malignant tumors, sarcoma of the tonsils is most important. It is 
usually of the lymphosarcomatous variety, and is rapid in growth 
and highly destructive. Epithelioma may occur at the base of the 
tongue, in the soft palate, or tonsils. Other varieties of cancer are rare. 

Polypoid tumors of the nasopharynx and hyperplastic adenoid 
growths of the same situation frequently extend downward into the 
pharynx proper. 

The Salivary Glands 

Inflammation of the salivary glands affects the parotid most fre- 
quently. 

Parotitis may be the expression of an independent infection (mumps) ; 
or may be secondary to various infectious diseases, such as typhoid 
fever, typhus fever, or pyemia. Parotitis sometimes occurs in associa- 
tion with diseases or injuries of the abdomen or pelvic organs. A reflex 
or "sympathetic" inflammation has been assumed as the cause of the 
parotid disease by some, but recent investigation seems to indicate 
that in all cases the real cause is infection through the duct. 

The specific cause of mumps has not been isolated (see page 354). 
The infection probably occurs through the parotid duct, and in some 
instances inflammations of the mucous membrane of this duct have 
been found to precede the parotitis. The gland is swollen and tensely 
distends its capsule. The inflammatory exudate is probably largely 
serous, as it may be absorbed and removed in the course of a very short 
time. The disease scarcely ever terminates in suppuration. Orchitis 
is an occasional complication, and may be followed by atrophy of the 
testes. 

The secondary parotitis occurring in the course of various infectious 
diseases is characterized by a marked tendency to abscess formation, 
and at all stages of the affection round-cell infiltration is conspicuous. 
After the formation of an abscess perforation may take place upon the 
cheek or into the mouth, and sometimes salivary fistulse (see below) are 
established. Chronic induration of the gland may remain after attacks 
of inflammation. Chronic parotitis may also result from certain intoxi- 
cations (lead, mercury, iodid of potash) or may occur in chronic nephritis 
or syphilis. Mikulicz described a form of simultaneous enlargement of 
the parotid, submaxillary, and lachrymal glands. The etiology is 
unknown. 

The submaxillary gland is occasionally affected with the parotid, or 
independently, in mumps. The sublingual gland rarely becomes in- 
flamed. 

Angina Ludovici, or Ludwig's angina, is a septic inflammation of 
the tissues of the floor of the mouth surrounding the submaxillary 
gland. It may result from carious processes at the roots of the teeth, 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



609 



or from infection of the submaxillary lymphatic glands in the course of 
various infectious diseases, particularly scarlet fever. The most frequent 
termination is abscess formation, with perforation externally or into 
the mouth. Occasionally rapid necrosis or gangrene results. Many 
different organisms have been found, but to none is ascribed any specific- 
importance. The characteristic of this affection is the density of the 
infiltration, there being almost a wooden hardness. The parts are dark 
red. 

Tumors. — The parotid gland is more frequently the seat of tumors 
than the other salivary glands. Benign tumors, such as fibroma, lipoma, 
or chondroma, are rare. The most common new growth is the so-called 
"mixed tumor," which is essentially sarcomatous, with the addition of 
fibroma, chondroma, or myxoma, and at times of all these. Some of 
the mixed tumors are said to be endotheliomata, but the decision is 
difficult because of the atypical growth of the glandular acini. Ade- 
noma and carcinoma are occasionally primary. 

Diseases of the Salivary Ducts. — Salivary fisiu las may result from 
traumatic injuries or from the perforation of abscesses. They most 
frequently affect the duct of the parotid. 

Concretions composed of phosphate and carbonate of calcium are 
occasionally observed, and may lead to obstruction of the ducts. 

Cystic dilatation of Steno's or Wharton's duct, or of those of the 
sublingual glands, may be due to concretions or to inflammatory proc- 
esses at the mouths of the ducts. Oval or elliptical tumors are formed, 
and contain transparent, viscid liquid. Such cysts belong to the group 
of conditions designated as ranula, but more frequently this is due to 
obstruction of the small mucous glands beneath the tongue. 

THE ESOPHAGUS 
CONGENITAL DEFECTS 

Occasionally the esophagus is double, being divided into two parts 
by a septum. Complete absence of the esophagus may occur in certain 
monstrosities; more frequently there is partial absence of the lumen 
about the middle of the tube. The lower end of the esophagus in such 
cases communicates with the trachea, while the upper end terminates 
as a blind pouch. The intermediate defective portion may be repre- 
sented by a fibromuscular cord, or may be entirely wanting. Fistulous 
communications may pass from the side of the neck to the upper end 
of the esophagus or pharynx. They are due to incomplete closure of 
the branchial clefts. 

CIRCULATORY DISTURBANCES 

Anemia may be due to general anemia; active hyperemia, to the 
irritation of hot liquids or chemicals. 

Passive congestion results from diseases of the heart or lungs, or 
from portal cirrhosis of the liver. In the latter condition large varicosi- 

39 



610 



A TEXT-BOOK OF PATHOLOGY 



ties may be established in the lower end of the esophagus, due to the 
communications between the left coronary vein of the stomach, the 
esophageal veins, and vena azygos. Hemorrhage may occur from these 
dilated veins, as they lie close beneath the mucous surface. 

INFLAMMATIONS 

Catarrhal esophagitis is characterized by hyperemia and desquama- 
tion of epithelium, with very little liquid secretion. It may be due to 
the ingestion of irritating acid or alkaline liquids, to scalding, or occa- 
sionally to direct traumatic irritation. Superficial erosions are some- 
times met with. 

Chronic catarrhal esophagitis is found in cases of passive conges- 
tion continued for a long time, and particularly in alcoholics. The 
mucous membrane is thickened and irregularly pigmented. Occasionally 
erosions are met with, and more commonly areas of hypertrophy of the 
mucosa. 

Pseudomembranous esophagitis may result from extension of 
pharyngeal diphtheria or pseudomembranous pharyngitis, or it may be 
primary in rare instances. 

Ulcerative esophagitis may occur as the result of pustular eruption 
in small-pox, or in consequence of irritation of foreign bodies. It is not 
unusual to find small or even large ulcers in the mucosa of esophageal 
diverticula. These are occasioned by the retention of food. Peptic 
ulcers similar to those occurring in the stomach are occasionally found 
in the lower end of the esophagus. 

Phlegmonous esophagitis is rare. It may result from the extension 
of intense inflammation of the mucous membrane into the submucous 
tissue, or to penetration of the mucosa by sharp points of fish-bones and 
the like. 

The inflammation arising after swallowing corrosive or irritant 
substances may partake of all the above forms. It is usually, with 
milder substances, a desquamative process, but these may penetrate and 
produce a pseudomembranous condition due to destruction and separa- 
tion of the mucosa. With the more corrosive agents a rapid necrosis of 
mucosa or even submucosa may occur, with later development of hemor- 
rhages or dry ulcers. Suppuration, diffuse or localized, may occur. 
Connective-tissue overgrowth leads to alterations in the lumen. After 
severe damage the whole thickness of the mucosa may not be restored, 
there being merely a coating of epithelium for the scar tissue. 

STENOSIS 

Stenosis of the esophagus may be due to the pressure of tumors 
or aneurysms upon the esophagus, to the lodgment of foreign bodies, 
to the growth of tumors in the esophageal walls, or to stricture of the 
esophagus. The last most frequently results from the healing of ulcera- 
tions caused by the swallowing of corrosive liquids. Syphilitic and 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



611 



posttyphoidal strictures are rare. Carcinoma of the esophagus may 
obstruct by the growth within or by the attendant contraction of the 
walls. Occasionally stenosis by malformation is congenital. 

Amite stenosis is a muscular spasm of the walls due to irritation, or 
as a part of hysteria or general convulsions. 



DILATATION 



Dilatation of the esophagus may occur in the form of a simple 
dilatation or ectasia, or in the form of diverticula. The former variety 
is common at the lower end of the esophagus, and is occasioned by ob- 
structions at the cardiac end of the stomach, or at the point where the 
esophagus passes through the diaphragm. The dilatation may reach 
considerable size. The mucous membrane is usually thin and often 
ulcerated. 

An "idiopathic form" has been described, in which there is more or 
less uniform or spindle-shaped widening, probably due to atony of the 
musculature or to vagus disease. Spasmodic contraction of the cardia 
is also described as a cause. 

Diverticula may be of two kinds, those 
due to pressure from within (pulsion diver- 
ticula) and those due to traction from with- 
out (traction diverticula) (Fig. 266). The 
former are more commonly found in the 
upper portion of the esophagus or the lower 
part of the pharynx, and arise from the 
posterior wall of the esophagus. They are 
due to thinning of the muscular coat and 
to hernia-like protrusion of the mucous 
membrane. They may reach considerable 
size by gradual distention. The traction 
diverticula are most frequently found near 
the lower end, opposite the bifurcation of 
the trachea. They are caused by adhesion 
of diseased bronchial glands and subsequent 
contraction of the attachments. They occupy 
the anterior wall of the esophagus and have a 
somewhat funnel shape. Perforation may occur, with the development 
of septic infection of the pleura, pericardium, or lungs. Perforation of 
the pulmonary arteries may lead to fatal hemorrhage. 




Fig. 266. — Traction divertic- 
ulum of the esophagus (modi- 
fied from Birch-Hirschfeld) . 



PERFORATION AND RUPTURE 

The esophagus may be perforated by necrotic or suppurative proc- 
esses surrounding it, or as the result of ulcers proceeding from within. 
Aneurysms of the thoracic aorta occasionally rupture into the esophagus. 
Retropharyngeal abscesses and phlegmonous inflammations of the 
deep cervical tissues may likewise discharge into the esophagus. Per- 



612 



A TEXT-BOOK OF PATHOLOGY 



foration by ulcers beginning within may be due to the lodgment of 
foreign bodies, or to the pressure of the cricoid cartilage in cases of 
great asthenia (see Pharynx). Perforation of the lower end of the 
esophagus may result from peptic ulcers or esophagomalacia due to 
regurgitation of gastric liquid either before or after death. Spon- 
taneous rupture of the esophagus occasionally 
takes place. In these cases there is doubtless 
always some antecedent weakness of the walls. 

INFECTIOUS DISEASES 

Tuberculosis of the esophagus is extremely 
rare, and most frequently results from extension 
of tuberculous adenitis of the bronchial glands. 

Syphilis occasionally occurs in the form of 
ulceration and cicatrization, leading to stenosis. 

Typhoid ulceration is probably more fre- 
quent than has been generally thought. Oc- 
casionally stenosis is caused by the cicatrices 
of the healed ulcers. 

Thrush may extend from the mucous mem- 
brane of the mouth and pharynx. 

Foreign bodies, like small bones, have been 
found embedded in the esophageal wall. 

TUMORS 

Fibroma, myoma, lipoma, or even sarcoma 
may occur as somewhat polypoid submucous 
tumors, but are rare. Papillomata, in the form 
of outgrowths of the mucous membrane, are 
more common. 

The most important tumor is carcinoma, 
which is usually found in the lower part, gener- 
ally at the position where the left bronchus crosses 
the esophagus, or near the passage of the tube 
through the diaphragm. It may, however, be 
found at any part. The squamous variety is the 
most common, though a few instances of glandular carcinoma are 
recorded. The tumor usually involves the entire lumen of the esophagus, 
projecting inward and forming irregular elevations of the mucous mem- 
brane. Later, the growth extends outward through the muscular coat 
to the fibrous outer layer, and even to the surrounding tissues. Dilata- 
tion occurs above the tumor, and occasionally perforation results from 
ulcerations caused by retained food. Local or more distant metastasis 
may take place. 

Cysts of the esophagus may occur. They are supposed to be due to 
misplaced lung or tracheal tissue. Many of them contain ciliated epi- 
thelial lining, strongly suggesting the latter origin. 




Fig. 267. — Carcinoma of 
upper end of esophagus 
(from a specimen in the 
collection of Dr. A. J. 
Smith). 



DISEASES OF THE GASTROINTESTINAL TRACT 



613 



The Stomach 
congenital defects 

Complete absence of the stomach has been found in certain mon- 
strosities; but stenosis or atresia of the pylorus, division by the forma- 
tion of septa, and hour-glass contractions have been more frequently 
observed. In cases of transposition of the viscera the stomach may be 
reversed in its position, the pylorus being on the left side, the cardiac 
end to the right. 

Congenital hypertrophic stenosis of the pylorus with or without 
dilatation of the stomach has been found more common than previously 
thought. The hypertrophy may affect either the pyloric mucosa or 
muscularis, or both. This is entirely apart from spastic stenosis of the 
pylorus in children, which has no anatomical basis. There may be some 
inflammation with the pyloric stenosis. 

There is occasionally a hypertrophy of the middle of the stomach 
wall which gives a picture somewhat like hour-glass stomach, and, of 
course, this condition can be simulated in later life by cicatricial con- 
traction. During digestion the midpiece of the organ contracts so far 
that there is a similarity to congenital hour-glass deformity. 

CIRCULATORY DISTURBANCES 

Anemia of the mucous membrane is found in cases of general anemia, 
particularly in pernicious anemia. The mucosa has an extremely 
pallid appearance, and is prone to undergo fatty degeneration and 
atrophy. 

Hyperemia. — Active congestion occurs in the beginning stages of in- 
flammation of the mucous membrane of the stomach, and results from 
irritating mechanical or chemical agents. The mucosa is bright red in 
color and may present minute hemorrhages. Moderate hyperemia is 
functional during the period of digestion. 

Passive hyperemia occurs as a result of obstructive heart disease or, 
more particularly, from obstruction of the portal circulation by cirrhosis 
or other diseases of the liver. Pulmonary affections, by interfering with 
the outflow of blood from the right side of the heart, may also occasion 
congestion of the stomach. The mucosa is dark red in color, swollen, 
and often edematous. Minute hemorrhages may occur, and small 
erosions may appear upon the surface. The changes are more marked 
near the pyloric end of the stomach. When the congestion has per- 
sisted for some time, dark reddish or bluish pigmentation, visually 
occurring in punctate form, is developed and chronic gastritis results. 

Hemorrhage in the mucous membrane or from the mucous mem- 
brane of the stomach results from a variety of causes. Small petechia? 
are met with in active or passive congestion and in acute inflammations, 
and they may follow thrombosis or embolism of the gastric vessels. 
Milder poisons cause them. They are also present in various infectious 



614 



A TEXT-BOOK OF PATHOLOGY 



or hemorrhagic diseases, such as purpura, scurvy, septicemia and the 
like, and in anemic affections like pernicious anemia. In many cases 
punctiform hemorrhages are developed just before death. 

These are all submucous hemorrhages, from the overlying mucosa 
of which the gastric juice may digest the covering, leaving erosions which 
may go on into distinct ulcerations. 

Larger hemorrhages, and particularly hemorrhages into the cavity 
of the stomach, result from intense passive congestion in cardiac dis- 
ease or cirrhosis of the liver, and from gastric ulceration or carcinoma. 
When large vessels have not been eroded the blood escapes gradually, 
and may be vomited in a semidigested and disorganized condition 
(coffee-ground vomit). This is peculiarly significant of carcinoma. 
When one of the larger vessels has been eroded, large quantities of fresh 
blood may be vomited and rapid death may occur. Occasionally hemor- 
rhage from the stomach in considerable quantity occurs in cases in which 
there is no visible lesion of the mucosa. 

Melarna neonatorum, the vomiting of blood by the newborn, results 
from gastric hemorrhage due to disturbances of circulation because of 
insufficient respiration, and possibly in other cases is a variety of infec- 
tious hemorrhagic disease. 

INFLAMMATION 

Acute inflammation of the mucosa, or acute gastritis, results 
from irritation by chemical, mechanical, or thermal agents. Some cases 
are doubtless due to infection. The mucous membrane is bright red 
and covered with more or less viscid mucous exudate. Punctate hemor- 
rhages may occur. Microscopically, there are found: marked mucous 
degeneration of the cylindrical cells of the tubules, and desquamation 
and granular degeneration of the cuboidal cells in the fundus of the 
glands. The mucous membrane between the tubules is infiltrated with 
round cells, and not rarely the same process occurs in the submucosa. 
The collections of lymphatic tissue (follicles) in the mucous membrane 
are often hyperplastic. Acute gastritis is more frequently found near 
the pyloric end than elsewhere. 

In considering the role of bacteria in the causation of gastritis it 
must be remembered that the bacteria normal to the stomach are 
few and not pathogenic. Most pathogenic bacteria are destroyed in the 
normal stomach. When, however, gastric mucosa and juice are altered 
by irritant poisons or by the fermentations and putrefactions arising 
in food taken to excess, especially in the presence of deficient propelling 
power by the muscular coat, the natural protective powers of the stom- 
ach are reduced. In such cases pathogenic germs introduced with the 
food thrive and attack the damaged walls. The normal flora comprises 
sarcinae, moulds, and yeasts. 

Pseudomembranous gastritis may result from the ingestion of cor- 
rosive poisons, and is occasionally seen in small-pox, typhus fever, and 
various forms of septicemia. It may be met with in diphtheria, and 



DISEASES OF THE GASTROINTESTINAL TRACT 



615 



may be due to direct extension of the process along the esophagus. 
The surface of the mucosa is covered with an irregular membrane, and 
necrosis and ulceration are not rarely observed, especially in cases due 
to corrosive poisons. 

Ulcerative Gastritis. — Small erosions may be found in cases of ex- 
treme congestion or petechial hemorrhage, as well as in acute gastritis. 
Actual ulceration is seen in pseudomembranous gastritis, and occa- 
sionally as a result of septic embolism in the mucosa in cases of malignant 
endocarditis. Infectious ulcerations occur in gastro-intestinal tubercu- 
losis, anthrax, and in typhoid fever, but are very rare. 

Chronic gastritis may result from repeated attacks of acute gas- 
tritis, and is especially prone to occur from improper habits of eating 
or from the abuse of alcohol. Chronic congestion, such as occurs in 
heart disease, strongly predisposes. 




Fig. 268. — Chronic gastritis, showing polypoid projections of the mucosa. 



Pathological Anatomy. — The appearance of the mucous membrane 
varies greatly. In the milder cases the surface is more or less irregular 
and granular, and is covered with mucous exudate. The color may be 
grayish, but in cases in which passive congestion has preceded the de- 
velopment of gastritis it is often slate colored from pigmentation. 

Microscopically, there may be found mucous degeneration of the 
cylindrical epithelium of the tubules, and desquamation and not rarely 
proliferation of the secretory epithelium in the fundus of the glands. 
The glands may be considerably dilated and filled with mucous exudate 
and desquamated cells. The interglandular tissues are infiltrated, 
and may be thickened by the formation of new connective tissue; the 
same process may involve the submucous coat. The blood-vessels of 
the latter are often greatly dilated and their walls may be thickened. 
In the later stages the glands may undergo progressive atrophy, the epi- 
thelium disappearing almost entirely and the lumen of the gland be- 



616 



A TEXT-BOOK OF PATHOLOGY 



coming less and less distinct. Coincidently with these changes, and to 
some extent causing them, there is fibrous overgrowth of the intergland- 
ular tissues. 

In some instances the contraction of the new-formed connective 
tissue causes protrusions of the mucous membrane or polypoid eleva- 
tions (Fig. 268). These may still further enlarge by proliferation and 
cystic distention of their glandular elements. In other cases the pro- 
liferative changes in the interglandular tissues may be more diffuse and 
the mucous membrane more regularly thickened. To both of these 
forms the name hypertrophic gastritis may be applied. In still other 
cases the formation of fibrous tissue causes pressure-atrophy of the 
glands; the surface in these cases becomes smooth and the mucosa 
greatly thinned (atrophic gastritis). 

The sclerotic process may involve not only the mucous membrane, 
but also the submucous and even the muscular coat. In such cases the 
thickness of the walls of the stomach may increase greatly, and the size 
of the organ greatly diminish by contraction. The terms interstitial 
gastritis, linitis gastrica, and leather-bottle stomach have been applied to 
such cases. It is sometimes difficult to distinguish such cases from 
diffuse scirrhous carcinoma. 

Pathological Physiology in Gastritis. — All forms of gastritis cause 
disturbances of the functions of the stomach, designated by the terms 
dyspepsia and indigestion. These disturbances are due to abnormal 
secretion of the gastric glands, reduced motor power of the walls of the 
stomach, and altered conditions of the nervous mechanism. The most 
important alteration of secretion is reduction of the amount of hydro- 
chloric acid. This is almost constant in uncomplicated gastritis; in some 
cases there is practically no hydrochloric acid reaction. The ferments, 
pepsin and curdling ferment, may be produced in insufficient amount, 
but are very rarely absent. In cases in which certain general conditions 
or nervous affections coexist with moderate gastritis, excess of hydro- 
chloric acid secretion occurs. Reduction in the amount of hydrochloric 
acid causes delay and inadequacy of digestion of proteins. When the 
acid is wholly wanting, decomposition of the proteins may occur, and 
sulphuretted hydrogen and other products of decomposition result. 
Excess of hydrochloric acid interferes with salivary digestion in the 
stomach, and, in consequence, fermentation of carbohydrates, with pro- 
duction of lactic, butyric, or acetic acid and of various gases, takes place. 
Such fermentation, however, is not, as a rule, observed unless the motor 
power of the stomach is deficient and the food is retained in the stomach 
beyond the usual time. It is not improbable that toxic substances are 
produced in some cases by protein decomposition, but accurate ob- 
servations are wanting. 

The motor power is usually deficient in proportion to the intensity 
of the gastric disease. In some cases the food is retained many hours 
longer than the usual periods, and fermentation and decomposition are 
thus greatly favored. Dilatation of the stomach may be brought about 
by the retention of food and the accumulation of gases of decomposition, 



DISEASES OF THE GASTROINTESTINAL TRACT 



617 



and the dilatation, in turn, increases the motor insufficiency of the 
wall. 

Altered conditions of the nervous mechanism of the stomach mani- 
fest themselves in a variety of ways. Sometimes there is excessive 
irritability of the mucosa, causing vomiting; in other cases a feeling of 
heaviness or pain. Alterations of appetite and of gastric motility are 
other results probably brought about, in part at least, through nervous 
disturbances. 

The general metabolism suffers profoundly in gastric disease- 
mainly in consequence of the insufficient food eaten or digested. Ema- 
ciation and systemic depression are the clinical consequences. It is 
possible that toxic substances produced in the stomach contribute to 
the metabolic disturbances, but this remains to be proved. 

GASTRIC ULCER 

Gastric, peptic, or round ulcers are roughly circular defects of the 
mucosa and part of the submucosa, probably due to the digestive action 
of the gastric juice upon a section of stomach wall previously deprived 
of its natural resistance. Similar lesions may occur in the upper end 
of the duodenum and in the lower end of the esophagus. Mayo has 
insisted that duodenal ulcers are much more frequent than has been 
heretofore believed, and that they are more common in men than in 
women. 

Etiology. — Many cases occur in young women suffering from chlorosis 
or anemia and general malnutrition, but the majority of peptic ulcers 
occur in males. The pathogenesis of these ulcers has occasioned 
much dispute. It is admitted that they are due to the action of the 
gastric juice upon parts of lowered vitality, and the term ulcus ex 
digestone is, therefore, appropriate. Increased acidity of the gastric 
juice is an undoubted factor. The lowered vitality which localizes 
the ulceration has been ascribed to many causes. Embolism or throm- 
bosis with infarction was suggested by the shape of the ulcers, and may 
be the explanation for some cases. Spasm of the blood-vessels in 
localized areas, possibly due to stimulation of the vagus, and thickening 
of the walls of the vessels, leading to anemia, have been suggested, as 
have also direct traumatic injuries of the mucous membrane and ex- 
ternal traumatism, causing rents of the mucous surface. Circulatory 
disturbances due to tight lacing are supposed by some to be important. 
When these peptic ulcers occur beyond the pylorus in the duodenum, 
they very rarely appear below where the intestinal contents are acid. 

For the chronic ulcers, alterations in the position and rugosity of 
the mucosa probably play a part. If the mucosa be thrown or drawn 
mechanically into abnormal folds the circulation is naturally altered 
and resistance to autodigestion decreased. Adhesions without may also 
have such a result. By some authors blood-vessel changes are held 
responsible, as arteriosclerosis, endo-arteritis, and thrombosis are 
exceedingly common in the vessels supplying the affected parts. It is 



618 



A TEXT-BOOK OF PATHOLOGY 



probably well at this time, when the question is as yet unsettled, to 
explain peptic ulcers as the result of the action of gastric juice, probably 
high in acidity, upon a small locality deprived of its resistance. The 
multiple benign ulcers seen in general infections or blood dyscrasias are 
doubtless of the same origin. They seldom if ever perforate, and give 
no symptoms. 

Gastric ulcers have been attributed to streptococcal embolism and 
thrombosis. Superficial ulcerations are said to occur if bile enter the 
stomach when there is 0.5 per cent, or more of hydrochloric acid present. 
Both of the above statements gain somewhat in value in view of the ex- 
perimental observations that streptococci are resistant to the antibac- 
terial action of the bile. Trypsin from the duodenal contents, entering 
an atonic stomach by reason of a relaxed pylorus, is said to have a potent 
effect on ulcer production. These observations by American workers 
may assist in clearing up the etiology of peptic ulcers. 




Fig. 269. — Peptic ulcer, showing erosion into a blood-vessel in the floor of the ulcer (Bol- 
linger) . 

Pathological Anatomy. — Peptic ulcers are usually single, but may be 
multiple. They are commonly situated in the lesser curvature and the 
posterior wall of the stomach, near the pylorus; occasionally they are 
found at the fundus or at the cardiac end. A striking form is the large 
saddle-shaped ulcer which has a narrow part in the lesser curvature 
and large spreading wings in the anterior and posterior wall of the 
stomach. They vary in diameter from a few millimeters to 3 or 5 
cm. Their shape is characteristic in that they have sloping edges, giving 
them a funnel form, with the apex toward the muscular coat. The 
shape corresponds to the distribution of the gastric arterioles. The edges 
may be irregular and rough, but are often, especially in older ulcers, quite 
smooth and rounded. 

Two dangers are always imminent — hemorrhage and perforation. 
Constant oozing of blood may be due to erosion of the surface, and 
larger hemorrhages may result from ulceration of one of the larger 



DISEASES OF THE GASTROINTESTINAL TRACT 



619 



arterial branches of the stomach (Fig. 269). Perforation is less common 
than hemorrhage. When the ulcer is situated posteriorly perforation 
is prevented by adhesions attaching the stomach to the head of the 
pancreas or other structures. When the ulcer is in the anterior wall per- 
foration is more liable to take place (Fig. 270). The rupture may occur 




Fig. 270. — Peptic ulcer with perforation (Bollinger). 



into the peritoneal cavity or into any of the surrounding structures, and 
fistulous communications may be established with the pleural or peri- 
cardial cavities, or even with the exterior through the abdominal walls. 
Abscesses of the liver, spleen, or pancreas may result from perforation 
into these organs. 




Fig. 271. — Stellate scar of a healed ulcer of the stomach (Bollinger). 

Microscopically, there is little to be seen aside from loss of surface 
tissue. In the older cases a slight circumferential fibrous tissue in- 
crease, especially at the thickened margin, may be found. 

In the healing of the ulcers scars are formed in the wall of the stom- 
ach. These have usually a rather characteristic stellate shape (Fig. 271). 



620 



A TEXT-BOOK OF PATHOLOGY 



In case of large ulcers extensive scars and considerable contraction of 
portions of the walls of the stomach result. Hour-glass contraction of 
the organ, or pyloric stenosis, may follow, and secondary changes, such 
as gastric dilatation, may ensue. Carcinomatous transformation is a 
not infrequent result of long-standing ulceration. 

ATROPHY AND DEGENERATIONS 

Atrophy of the glands or gastric tubules is frequently seen in chronic 
gastritis. The same condition occurs as a senile change and in asso- 
ciation with various chronic diseases, especially pernicious anemia. A 
certain amount of atrophy of the entire mucous membrane results in a 
purely mechanical way from gastric dilatation. 

Decrease in the size of the stomach as a whole may be the result 
of chronic gastritis, when the new-formed connective tissue contracts. 
In such cases the stomach may become quite small, the walls, however, 
increasing in thickness. Somewhat similar shrinkage in the size of the 
stomach occurs in some instances of infiltrating cancer of the stomach. 
The tumor may involve all parts of the organ equally, and cause more 
or less thickening of its walls, but the size of the organ is diminished by 
contraction of the connective tissues. 

A form of true atrophy is sometimes caused by obstruction of the 
cardiac orifice ; it is probably due, in part at least, to the insufficiency of 
food admitted to the stomach. 

Degenerations of the mucous membrane of the stomach are met 
with either in association with inflammation or as independent affec- 
tions. 

Fatty degeneration of the epithelial cells of the glands may be the 
result of intoxications (phosphorus, arsenic), or of conditions such as 
those which lead to simple atrophy. The occurrence of atrophy and fatty 
degeneration of the gastric tubules in cases of pernicious anemia is of 
great importance, though it remains unsettled whether these conditions 
are the cause or result of the anemia. 

Pigmentation is met with as a result of chronic congestion or hemor- 
rhage into the mucous membrane. The mucosa has a dark red or often 
a slaty discoloration, which is prone to be distributed in lines or in cir- 
cumscribed patches. Bluish pigmentation of the stomach sometimes 
occurs from the ingestion of silver. 

Amyloid infiltration may be found around the blood-vessels of the 
submucosa, or more rarely of the mucosa itself, in cases of general amy- 
loid disease. Amyloid ulcerations may occur. 

Calcification has been met with in cases of bone disease with sur- 
charge of the blood with earthy salts. It appears in the form of scales or 
plates of calcification upon the mucosa. 

Gastromalacia, or simple softening of the walls of the stomach, is 
usually a postmortem condition, and is due to the action of the gastric 
juice. The nature of this process has occasioned much discussion, but it 
is now recognized as a postmortem condition, or as a condition occurring 



DISEASES OF THE GASTROINTESTINAL TRACT 621 

during life only in the agonal period. It affects the fundus or posterior 
part of the stomach. The mucous membrane becomes soft and more 
or less gelatinous, and is grayish or yellowish in color if the mucosa was 
anemic, or brownish in cases in which there was congestion before 
death. Rupture and discharge of the contents of the stomach into the 
peritoneal cavity, spleen, or other adjacent organs may occur. The 
walls of the stomach in the affected area show granular degeneration of 
the component cells, but no evidences of inflammatory reaction, and 
when rupture has occurred there are no reactive inflammatory lesions 
of the peritoneum, showing that the perforation occurred after death. 

ALTERATIONS IN POSITION AND SIZE 

Alterations in Position. — The stomach may be displaced into the 
thoracic cavity in cases of perforation or rupture of the diaphragm 
(diaphragmatic hernia). It may be displaced anteriorly as a congenital 
malposition in consequence of defects of the anterior abdominal walls, 
and may in such cases be quite exposed. Downward dislocation, or 
gastroptosis, is either congenital or acquired. The acquired form may be 
due to diseases of the stomach, particularly dilatation, to the traction of 
inflammatory adhesions, to enlargement of the spleen, and probably to 
tight lacing. Occasionally in anemic and relaxed women all of the ab- 
dominal viscera tend to descend (splanchnoptosis). 

Dilatation, or gastrectasia, most frequently results from obstruction 
of the pylorus. The latter may be due to cicatrization the result of the 
healing of ulcers, to fibroid overgrowth and contraction the result of 
chronic gastritis, or to pyloric carcinoma. The pressure of tumors, of a 
movable kidney, or of aneurysms may act similarly. At first, pyloric 
stenosis may be compensated by hypertrophy of the muscular layer of 
the stomach, but soon dilatation occurs; food stagnates, fermentation 
takes place, and the dilatation is increased. The mucosa becomes thin 
and ofttimes degenerated and atrophic, the exact changes being those 
of the specific variety of gastritis existing. 

A second group of cases (atonic dilatation) is independent of stenosis 
of the pylorus, but due to weakness of the walls of the stomach. The 
latter may be the result of chronic gastritis or of a general atonic state. 
Constant overeating may play an important part in some cases. Finally, 
dilatation may result mechanically from abnormal adhesions of the 
stomach. 

Dilatation of the stomach occasions great stagnation of food and, 
in consequence, imperfect digestion and decomposition of the food. 
When hydrochloric acid is absent (as in cancerous stenosis of the pylorus 
and marked atonic dilatation) lactic acid fermentation is pronounced; 
when hydrochloric acid is present lactic acid is less abundant or absent. 
Sulphuretted hydrogen and inflammable gases are occasionally formed, 
especially in cases in which hydrochloric acid is present. The mucous 
membrane of dilated stomachs loses its absorptive power to a large de- 
gree. This, together with the retention of ingested liquid in the stom- 



622 



A TEXT-BOOK OF PATHOLOGY 



ach and the consequent lessening of intestinal absorption, leads to great 
emaciation, and especially to desiccation of the tissues. The muscu- 
laris shows hyaline change and thinning, with elongation of the fibers. 
The mucosa shows atrophic glands, with fatty cells. 

Among the micro-organisms met with in the gastric contents the 
Sarcince ventriculi are of interest. These occur in bundles of peculiar 
square form. The sarcina is more frequent in non-cancerous than in 
cancerous dilatation. In cases of dilatation due to cancer of the stom- 
ach the Oppler-Boas bacillus is found (see below). 

An acute form of gastric dilatation sometimes occurs after anes- 
thesia, following indiscretions in diet, as a result of pressure on the duo- 
denum when the mesentery is pulled upon by twists of the intestine, 
after traumatism, and at times without demonstrable cause. The most 
frequent anatomical factor is twisting of the intestinal loops, especially 
in the presence of an abnormally long mesentery. The method of action 
of these causes is not clear, but they probably operate by paralyzing the 
gastric wall. 

INFECTIOUS DISEASES 

A few cases of tuberculous ulceration have been recorded, and syph- 
ilitic gummata or ulceration may occur. The tuberculous processes may 
be hematogenic or localized, in which latter case they are secondary to 
peptic ulcer; they assume a ragged, punched-out appearance and seldom 
perforate. Diffuse cirrhosis and ordinary gastritis may be dependent 
upon syphilis, but the etiological connection is uncertain. Anthrax may 
lead to necrotic and hemorrhagic ulcers of the mucosa. Thrush is 
rarely met with, though the spores of the saccharomyces are frequently 
present in the stomach when the mouth is affected. 

TUMORS 

Connective=tissue Tumors. — Fibroma, myoma, and lipoma are occa- 
sionally met with as submucous or subserous polypoidal tumors. Sar- 
coma is rare. It affects the lymphoid tissues of the deeper parts of the 
mucosa, and rapidly spreads to the submucosa. Most cases are of the 
round-cell variety. Lymphoid infiltrates of the adenoid tissues of the 
stomach may be one of the lesions of leukemia or Hodgkin's disease. 

Epithelial Tumors. — Polypoid elevations, sometimes with cystic en- 
largement of the glands, occur as a result of chronic inflammation, and 
may be large enough to be regarded as tumors in a clinical sense. Adeno- 
matous proliferation of the glands is met with in the form of irregular, 
flat tumors, but these so rapidly become carcinomatous that pure ade- 
noma scarcely exists. 

Carcinoma is the most frequent tumor of the stomach. It occurs 
at middle age, and more often in the male sex than in the female. 
The pyloric end of the organ and the lesser curvature are the favorite 
sites, but other parts may be affected and the entire organ may be in- 
volved. Cancer of the stomach may appear as a ring-like swelling of the 



DISEASES OF THE GASTROINTESTINAL TRACT 



623 



mucous membrane and submucous tissue, surrounding the pylorus and 
causing stenosis; as more or less circular, flat elevations in the lesser 
curvature or elsewhere; and, finally, as a diffuse infiltration of the mu- 
cosa, submucosa, or all of the coats of the entire organ. The mucous 
surface is generally irregularly elevated, and tends to become ulcerated, 
especially in medullary cancer and in the cases in which there are local- 
ized flat elevations. Sometimes portions of the cancerous tissue may 
be found in the vomitus, and the diagnosis of the disease may be thus 
established (Fig. 272). Perforation of the wall of the stomach may 
result from necrotic and ulcerative processes (Fig. 273) . The neighbor- 
ing lymphatic glands, especially those in the lesser curvature of the 



Fig. 272. — Fragment of carcinomatous tissue found in stomach-washings (Reinevoth). 

stomach, are usually implicated through the lymphatic vessels. Direct 
extension to the peritoneum may occur, especially in cases of colloid 
cancer; and metastasis through the blood-vessels is extremely common. 
Cancerous emboli are frequently found in the portal radicles within 
the liver, and multiple cancer-nodes of the liver are usually found in 
cases which have existed for some length of time. Hematogenous 
metastasis is most common in soft, ulcerating cancers. 

Varieties. — There may be distinguished hard or scirrhous cancers, 
soft or medullary cancers, adenocarcinomata or malignant adenomata, and 
cylindrical-celled or squanious-celled carcinomata. All forms begin in 
the mucous membrane and spread to the submucosa. The muscu- 




624 



A TEXT-BOOK OF PATHOLOGY 



laris may be penetrated and infiltration of the serosa, or even of sur- 
rounding tissues, may be observed. 

Scirrhous cancer may appear as a circular constricting new growth 
at the pylorus (Fig. 274). In other cases the disease is extensive, and 




Fig. 273. — Carcinoma of the cardiac end of the stomach; extension into duodenum: S, 
Dilated esophagus; K, ulcerated carcinoma; G, a perforating ulceration; M, stomach 
(Orth). 

the entire organ may be involved by uniform infiltration, and macro- 
scopically the appearance of a simple cirrhosis of the stomach is pre- 
sented. In the last-mentioned variety the organ may be greatly reduced 
in size, though the walls are greatly thickened. The mucous surface 
rarely ulcerates in scirrhus. 




Fig. 274. — Scirrhus of the pylorus, causing pyloric stenosis: D, Duodenum; P, pylorus; 
K, carcinomatous projections on the mucosa (Orth). 

Medullary or soft cancer usually appears as a localized tumor at 
the pylorus or in the lesser curvature. The mucous membrane is irreg- 
ularly elevated, ofttimes in a cauliflower manner (Fig. 275). Ulcera- 
tion on the surface is common, and hemorrhagic extravasation into the 



DISEASES OF THE GASTROINTESTINAL TRACT 



625 



stomach is, therefore, frequent. Metastasis through the blood is liable 
to occur. Complete perforation of the stomach may take place. 

Malignant adenoma, or adenocarcinoma, begins as a proliferation 
of gastric tubules. The new-formed acini are, however, atypical in 
arrangement and number, and there is a tendency to conversion of the 
normal cylindrical cells into cuboidal cells, and to extensive cancerous 
infiltration by excessive formation of acini or tubules, as well as by de- 
struction of the basement-membrane of the acini and irregular cellular 
invasion. The appearance of the tumor and its tendencies are the same 
as those of soft cancer. 

Cylindrical cancer, or cylindrical epithelioma, probably arises 
from the cylindrical lining cells of the stomach, or from the cells in the 
upper parts of the tubules. Atypical tubular aggregations of cylindrical 
cells with a tendency to conversion into cuboidal cells are observed. 
The pylorus is the common seat. 




Fig. 275. — Cauliflower carcinoma of pylorus: M, Stomach; P, pylorus; D, duodenum 

(Orth). 

Squamous cancer occurs at the cardiac end, and generally in asso- 
ciation with carcinoma of the lower end of the esophagus, from which 
the squamous epithelium extends a short distance into the stomach. 
It is rare. 

Colloid cancer of the stomach appears as a localized or, more fre- 
quently, diffuse infiltrating, gelatinous new growth of the mucosa and 
submucosa. Rapid extension through the walls of the stomach and to 
the peritoneum is frequent. The cells and the stroma of the tumor 
show myxomatous degeneration; and the epithelial elements may in 
the later stages entirely disappear. Extensive invasion of the perito- 
neum is not infrequent. 

Pathological Physiology and Results. — Carcinoma of the stomach 
is most frequently situated at or near the pylorus, and, therefore, inter- 
feres with the propulsion of food. Stagnation of the stomach contents 
and fermentation result. The latter is favored by the absence of hydro- 
chloric acid secretion so habitually observed. In consequence of the 

40 



626 



A TEXT-BOOK OF PATHOLOGY 



stagnation the stomach dilates and may reach enormous size, not rarely 
filling a large part of the abdominal cavity. Lactic acid fermentation is 
frequently pronounced. Disturbances of metabolism, with loss of flesh 
and strength, are marked. Among the micro-organisms present in the 
stomach contents a long, thread-like bacillus (Oppler-Boas) has at- 
tracted much attention, and has been supposed by some to occur only 
in cancer of the stomach. It is certainly frequent, but just as certainly 
not peculiar to the disease. 

THE INTESTINES 
CONGENITAL AND ACQUIRED ABNORMALITIES 

Occasionally total absence of large parts of the intestinal tract is 
found in monstrosities. Lesser defects, leading to narrowing or dis- 
tortion of the intestines, are more frequent. Marked developmental de- 
fects most frequently occur in the rectum, which may be completely 
absent, or may be obliterated at the lower end. In such cases there may 
be fistulous communications with the urogenital tract, or there may be 
a persistent cloaca, as in fetal life. 

Congenital Enlargement of the I ntestines. — The colon is most apt 
to be affected, and may be greatly enlarged, the most important exam- 
ple of which is Hirschsprung's disease or megacolon. This may affect 
the whole colon or only the descending part. By some, atony or incom- 
pletion of the musculature is held responsible, while others look upon it 
as obstructive from abnormalities in the mesocolon. 

Diverticula. — Localized dilatations, constituting diverticula, are 
frequent, the most common form being Meckel's diverticulum. This 
usually arises from the ileum, about 1 meter above the ileocecal 
valve, and is attached to the intestine opposite the mesentery. It 
represents the remains of the omphalomesenteric duct of fetal life. 
Occasionally it has been found patulous to the umbilicus. More 
commonly there is merely a short diverticulum of the intestines, vary- 
ing from a few to several centimeters in length, and having a closed 
extremity which may be somewhat dilated. The extremity may be 
connected with the umbilicus by a cord, but is usually free. 

Diverticula are also formed in later life. Very commonly, in cases 
of constipation, small pouchings or dilatations occur in the large intes- 
tine, particularly in the descending colon and rectum. Another form 
affects the small intestine more commonly than the large bowel. In 
this there are found small pouches lying near the mesenteric attach- 
ment, and owing their origin to localized weakness or separation of the 
muscle-fibers of the bowel. Protrusion of the mucosa takes place, prob- 
ably as a result of pressure from within; and the pouch is, therefore, a 
hernia-like projection of the mucosa and serosa through separated mus- 
cular fibers. Such diverticula may be multiple or single. 

The importance of the diverticula, especially the Meckel variety, 
is that they may be involved in inflammation which may lead to per- 



DISEASES OF THE GASTROINTESTINAL TRACT 



627 



foration or to adhesions. In the latter case coils of intestines may be 
constricted and lead to ileus. Meckel's diverticulum, when not inflamed 
but if attached at the umbilicus, sometimes catches a knuckle of gut and 
leads to intestinal obstruction. 

Congenital Abnormalities in Position. — The position of the several 
parts of the intestinal tract may vary widely from the normal. Not 
rarely the ascending colon and cecum are situated on the left side; the 
sigmoid flexure and descending colon being on the right side. 

Cecum mobile is an abnormal looseness of cecum, sometimes leading 
to surgical conditions in this organ or the appendix. 

Enterocystoma. — A congenital cystic condition found at the um- 
bilicus has been described as cystic dilatation of parts of the original 
omphalomesenteric system of the fetus, and has been named "entero- 
cystoma." 

Dilatation. — More or less uniform enlargement of the intestines 
may result from long-standing constipation. Enormous dilatation of 
the colon is sometimes seen. In this the wall of the intestine undergoes 
compensatory hypertrophy, and small pouchings or diverticula are 
commonly observed, especially in the rectum. 

This is the chronic dilatation. Acute dilatation is due to sudden 
obstruction, as from a foreign body or by paresis of the muscular wall, 
as occurs by blows on the abdomen. Again, the dilatation may be acute, 
but not necessarily sudden, when the gut walls are paralyzed by peri- 
tonitis or by toxins of diseases not localized to the abdomen (menin- 
gitis). Acute dilatation occurs in surgical shock. 

Narrowing, or stenosis, of the intestine at any part may be due 
to pressure of new growths or displaced viscera, to cicatricial constric- 
tions following ulcerations, or to neoplasms. Cicatricial stenosis is par- 
ticularly common in the rectum following dysenteric or syphilitic ulcers. 
Narrowing of the lumen may be due to an ingrowth of carcinoma or 
the presence of papillomatous or polypoid tumors within. 

Hernia. — This term is applied to malposition of any of the viscera, 
with displacement of the organ from the cavity in which it normally 
lies; but it has been more particularly applied to such displacements of 
the intestines, and the single term "hernia" is significant of intestinal 
hernia. 

Occasionally hernise are congenital; more often they are acquired. 
Hernia occurs at the points where the abdominal wall or the peritoneum 
is naturally weak from the emergence of vessels or the existence of natu- 
ral outlets, or has become weakened by injury or surgical operation. 

Etiology. — The predisposition to hernia may consist in unnatural 
weakness of the abdominal wall, especially at the points where hernia 
is likely to occur, resulting from imperfect closure of such portions or 
from general muscular weakness. Abnormal movability of the intes- 
tines, resulting from natural or acquired elongation of the mesenteric 
attachments and increased weight of the abdominal contents from the 
deposit of peritoneal fat, contributes largely to the formation of hernia?. 
The immediate exciting cause in many cases is strain, and probably in all 



628 



A TEXT-BOOK OF PATHOLOGY 



cases repeated strain helps in the development of the protrusion. The 
most frequent form of ventral hernia is the umbilical, which occurs 
especially in infants as the result of imperfect closure of the abdominal 
walls at the umbilicus. 

There may be distinguished two groups or varieties — the internal 
and the external hernias. 

Internal Hernia. — By this term are designated hernia-like displace- 
ments of the intestines into other cavities within the body, the most im- 
portant being upward displacement into the thorax through congenital 
or acquired clefts of the diaphragm {diaphragmatic hernia); and back- 
ward displacement through the peritoneum into the retroperitoneal 
space {retroperitoneal hernia). 

External hernia may be inguinal, femoral, ventral, vaginal, rectal, 
perineal, ischiatic, or obturator. The most frequent of these are the in- 
guinal and the femoral. In the former the protrusion may occur through 
the external inguinal ring, the intestine descending through the in- 
guinal canal, sometimes as far as the scrotum {indirect inguinal hernia). 
In another group of cases the intestine pushes directly forward through 
the abdominal wall and external inguinal ring, and may present ante- 
riorly under the skin, or may descend through the lower part of the 
inguinal canal to the scrotum {direct inguinal hernia) . The indirect 
inguinal hernise are sometimes congenital, and are due to the failure of 
closure of the peritoneal reflection which passes downward through the 
inguinal canal. 

Femoral hernise are especially common in women, and are formed by 
protrusion of the intestine through the femoral ring, the hernia present- 
ing on the inner side of the thigh, at the position of the saphenous opening. 

Pathological Anatomy. — The hernia consists of a sac or wall and 
of the contents of the hernia. The sac is usually constricted at 
its junction with the general peritoneal cavity (neck), and distended 
and dilated outside of or below this point (fundus or body of sac). 
The sac of the hernia is always lined with the protruded portion of the 
peritoneum. The contents of the hernia may be coils of intestine or 
portions of omentum, or both. Most frequently some part of the small 
intestine occupies the hernia, and sometimes simply a Meckel's diver- 
ticulum has been discovered. In rare cases the sigmoid flexure or other 
parts of the great bowel may be found. 

Secondary changes often ensue. Inflammation of the lining mem- 
brane of the sac and of the intestinal coils may lead to fibrous adhesions 
constricting the neck of the sac and binding the intestines firmly in 
place. If the contents of the hernia have receded, such inflammation 
may obliterate the sac completely or merely at its neck, the body of the 
sac in the latter case becoming distended with serous liquid. In cases 
in which portions of omentum are included in the hernia, hypertrophic 
overgrowth of the adipose tissue may occur, and may lead to appear- 
ances not unlike those of a lipoma. 

Hernias are described as being reducible and irreducible, according 
to the ability of replacing the contents into the peritoneal cavity or not. 



DISEASES OF THE GASTROINTESTINAL TRACT 



629 



Hernise become irreducible when the coils of intestine are distended by the 
accumulation of fecal matter, when fibrous adhesions have narrowed the 
neck of the sac or bound the coils firmly in place, or when additional coils 
of intestine or portions of the omentum have descended into the hernia. 

Strangulated Hernia. — This term is applied to hernise in which pres- 
sure at the neck by inflammatory exudation or constriction, or in- 
veterate obstruction by accumulating contents of the bowel, has led 
to obstruction of the circulation in the intestinal coils of the hernia. 
Intense passive congestion, inflammation of the peritoneal covering 
of the intestines within the hernia, and, finally, gangrenous necrosis 
are the frequent results. 

INTESTINAL OBSTRUCTION 

Complete obstruction of the intestines, or ileus, may be due to in- 
ternal strangulation by bands of adhesions, to a twist or volvulus, or to 
intussusception or invagination. 

Internal strangulation may be due to the obstruction of a coil of 
intestine by fibrous peritoneal adhesions, or by a coil slipping through 
abnormal openings or perforations in the mesentery or omentum. The 
persistence of the cord passing from the end of a Meckel's diverticulum 
to the umbilicus is an unusual cause. 

The results of internal strangulation are generally serious. Great 
dilatation occurs above the point of obstruction, the intestine below 
becoming collapsed. Great congestion and subsequently peritonitis 
occur at the point of stricture, and necrosis with perforation may ensue. 
The constitutional symptoms may be due to absorption of toxic sub- 
stances developed in the strangulated parts, that is, in the gut walls 
by autolysis. The results are essentially the same for obstruction of 
all parts of the intestines, but appear more rapidly when the upper 
parts are affected. The loss of water is due to drainage of large 
quantities into the gut lumen. These theories hold for all forms of 
obstruction, including the postoperative intestinal paresis. 

Volvulus is the term applied to a twist of some part of the intestinal 
canal. Occasionally there is simple rotation of the bowel about its own 
axis, but more commonly a loop of intestine twists about on its mesenteric 
attachment. Abnormal laxity of the mesentery is an important pre- 
disposing cause, and may be a congenital condition, or may result from 
the absorption of fatty deposit between the mesenteric layers. The 
immediate cause is generally strain or abdominal compression. 

The most frequent seat of volvulus is the sigmoid flexure. The 
bowel above the point of obstruction becomes distended, as in internal 
strangulation, while the coil included in the twist itself is engorged 
with blood and often presents hemorrhagic infarctions in consequence 
of obstruction of the veins in the mesentery. Gangrene of the bowel 
may result. Complete knots are occasionally observed in volvulus. 

Intussusception, or invagination, is a condition in which one part 
of intestine slips into an adjoining part, as one may invert the finger 
of a glove (Fig. 276). The upper part of the intestine is usually indu- 



630 



A TEXT-BOOK OF PATHOLOGY 



plicated and pushed into the lower part. Irregular peristalsis, resulting 
from intestinal disorders, and particularly from atony of one part with 
increased activity of adjoining parts, is the most frequent cause, and con- 
tinuing in the disturbed part further propels the outer over the inner 
segment, or vice versa, as it would a mass of feces. Occasionally poly- 
poid tumors within the bowel are dragged forward by the peristalsis, 
and carry the higher part of the intestine to which they are attached 
into the lower part. Intussusception is more 
common in children than in adults, and affects 
the ileocecal region most commonly. Not infre- 
quently multiple invaginations are found in the 
small intestine of children; these probably occur 
during the death agony or postmortem. 

The portion of the gut slipping into the re- 
ceiving part is called the intussusceptum; the 
outer or receiving section, the intussuscipiens. 

The appearance of intussusception is simply 
that of one part of intestine pushed into the ad- 
joining part, with secondary inflammatory and 
congestive changes. Most frequently invagina- 
tion begins at the ileocecal region, the valve and 
ileum being carried forward into the ascending 
colon. Very rarely the ileum itself invaginates 
through the valve. The attachment of the mesen- 
tery leads to a sharp angulation of the area of in- 
vagination, and the extent to which the protrusion 
may occur will depend upon the length of the 
mesentery. Occasionally the ileocecal valve may 
be carried through the colon and rectum and 
present externally. The adjoining serous surfaces 
of the invagination tend to unite by peritonitis, 
and the intussuscepted portion may become gan- 
grenous and be discharged with re-establishment of the lumen. If 
peritonitis has established union between the ensheathed and the en- 
sheathing section of the gut, recovery may ensue. Otherwise perfora- 
tion leads to fatal peritonitis. 



Fig. 276. — Intussus- 
ception (from a speci- 
men in the Museum of 
the Philadelphia Hospi- 
tal). 



PROLAPSE OF THE RECTUM 

Prolapse of the rectum in consequence of weakness of the sphincter 
and other parts of the wall, together with repeated straining, is a 
common condition in infants, and is occasionally met with in adults. 
In children any form of diarrhea may be complicated by prolapse; in 
adults chronic proctitis is the most frequent cause. The weakened con- 
dition of the sphincter in proctitis furnishes the predisposition, and the 
characteristic tenesmus of the disease is the immediate cause. Prolapse 
may be only an occasional condition, or may be constant. Secondary 
inflammation, ulceration, and even necrosis of the prolapsed portion 
may occur. 



DISEASES OF THE GASTROINTESTINAL TRACT 



631 



ATROPHY AND DEGENERATIONS 

Atrophy of the mucosa is frequently met with as a part of chronic 
enteritis in its later stages. This is especially marked in young children 
suffering from chronic intestinal catarrh and marasmus. Occasionally 
atrophy of the mucosa or of all of the coats of the intestines may occur 
as an independent affection, or as the result of marantic or cachectic 
conditions. 

Pigmentation may be due to hemorrhages in the mucosa or sub- 
mucosa, and not infrequently after intense hemorrhagic inflammation 
the bowel may be quite black from the deposit of hematogenous pig- 
ment. Brownish pigment deposited in the muscle-cells, analogous to 
that of brown atrophy of the heart, is occasionally observed in old and 
cachectic individuals. Similar pigmentation of the muscle-cells and 
also of the submucosa or mucosa, of even more decided character, occurs 
in youthful persons addicted to alcohol. The intestines alone may be 
thus affected, or the liver, spleen, lymphatic glands, and skin are simul- 
taneously involved. The term hemochromatosis (q. v.) has been proposed 
for this condition. It is said that pigmentation of the colon may re- 
sult from absorption of bile derivatives. Pick accounts for some of the 
obscure pigmentations of the colonic mucosa by assuming a deposit of 
melanin-like bodies, probably protein digestion products under the in- 
fluence of tyrosinase. 

Amyloid infiltration is met with in association with amyloid dis- 
ease of the liver, kidneys, or spleen, and particularly in cases in which 
there is tuberculous ulceration of the intestines. The mucous mem- 
brane is principally involved, and becomes somewhat hardened and pre- 
sents a peculiar grayish luster. Superficial erosions and even ulcers 
may result. The process begins, as elsewhere, in and around the small 
blood-vessels. 

CIRCULATORY DISTURBANCES 

Active hyperemia may occur from acute irritation, and forms a 
part of inflammation. 

Passive hyperemia results from causes similar to those producing 
congestion of the stomach. Among these, obstructive diseases of the 
liver, notably cirrhosis, and cardiac and pulmonary affections are most 
prominent. The intestinal mucosa becomes somewhat swollen, ofttimes 
edematous, dark bluish-red in color, and occasionally marked by punc- 
tate hemorrhages. The mesenteric veins are widely dilated. Occasion- 
ally hemorrhagic liquid is found within the intestines, the points of 
hemorrhage remaining undiscovered. 

Hemorrhage. — Petechia? are found in many cases of violent septic 
or infectious diseases, in intense anemias, and as the result of marked 
passive hyperemia. Embolism in cases of ulcerative or malignant endo- 
carditis may lead to petechial hemorrhages, and the same are observed 
as a part of the morbid anatomy of intestinal anthrax. Large intestinal 
hemorrhages may occur from typhoid, tuberculous, dysenteric, or syph- 



632 



A TEXT-BOOK OF PATHOLOGY 



ilitic ulcerations, or from the perforation of a large arterial branch by a 
peptic ulcer in the duodenum. Hemorrhoids may occasion consider- 
able hemorrhages from the rectum. 

Edema of the mucosa may result from passive congestion, and at- 
tends acute or chronic inflammations, especially the more intense forms. 

Embolism and thrombosis of the mesenteric arteries are rare 
conditions, due most often to cardiac embolism, but also to arteriosclero- 
sis in loco and to downward thrombosis from the portal vein. Embolism 
may lead to hemorrhagic infarction because of some inadequacy of the 
anastomosis of the mesenteric vessels, which usually is rich. The re- 
sult is a stretch of paralyzed, reddened, and swollen gut within which 
hemorrhage and, later, sloughing occur, corresponding to the distribu- 
tion of the occluded vessel. 

Hemorrhoids result from varicose enlargement of the veins of the 
rectum. They are usually found in the lower part of the rectum, 
inside or outside the sphincter, and a distinction is made between in- 
ternal and external hemorrhoids. 

Etiology. — Obstruction of the venous circulation is the important eti- 
ological factor. It may be due to chronic diseases of the liver (cirrhosis), 
repeated pregnancies, pelvic tumors, or chronic constipation with fre- 
quent retention of feces in the rectum. The last-named condition acts 
in a twofold manner. On the one hand, it causes venous obstruction, 
and, on the other hand, chronic proctitis, which in turn occasions disease 
of the veins of the rectum, and thus predisposes them to dilatation. In 
all cases of hemorrhoids, constipation and the resulting proctitis are 
important as auxiliary causes. The anal veins are poorly supported by 
connective tissue, so that when the sphincter contracts it holds the blood 
within the distended vessels. Hemorrhoids are rarely met with before 
adult age. 

Pathological Anatomy. — The hemorrhoid presents itself as a small 
polypoid elevation of more or less congested appearance. On section it 
is found to be highly vascular and to consist of dilated veins. There 
may be a congeries of slightly enlarged veins or cavities of considerable 
size. Between the veins there is more or less abundant inflammatory 
connective tissue. Thrombosis often occurs within the cavities; and 
occasionally the fibrous tissue around them undergoes active prolifera- 
tion, when a structure resembling a fibro-angioma results. Hemorrhagic 
extravasations may occur from the veins, and free hemorrhage from the 
surface is a common symptom. Infective inflammation and phlebitis of 
the veins sometimes occur, in which cases the hemorrhoid enlarges 
and becomes inflamed and edematous. Inflammation of the adjoining 
tissues may occur (proctitis, periproctitis). 

Hemorrhoids may cause marked anemia by the repeated hemor- 
rhages, and sometimes occasion septic infections when they have them- 
selves become infected and inflamed. 

Other varices may arise in the intestines, as, for example, in cirrhosis 
of the liver. 



DISEASES OF THE GASTROINTESTINAL TRACT 



633 



INFLAMMATIONS 

Inflammation of the intestines, or enteritis, may affect any part 
of the intestinal canal, and involve the mucosa and submucosa more 
particularly. It is more frequently present in children and in the aged 
than at other periods of life. 

Etiology. — The causes of enteritis are similar to those of gastritis, 
and among them may be reckoned all forms of irritating foods or foreign 
matter taken with the food. Poisons of various kinds operate in a 
similar manner. In many cases the irritant poisons which occasion 
enteritis are developed within the body in consequence of improper 
digestion and fermentation. Bacteria play an important role in this 
process, and are themselves the direct cause of enteritis in instances in 
which improprieties of diet or digestive disturbances have furnished 
favorable conditions for their growth and multiplication. The normal 
colon bacillus is perhaps the most frequent and important micro- 
organism of ordinary non-specific enteritis, but other organisms doubt- 
less frequently play a part. The colon bacillus probably increases in 
virulence under certain conditions and then occasions irritation. 

The bacteria of the intestines comprise many species, chiefly sapro- 
phytic, but which may under appropriate circumstances cause enteritis. 
They are engaged in fermentation and putrefaction, the two forces being 
balanced in the normal state. When, however, one or the other is ex- 
cessive, it reduces the natural protective forces. The normal intestinal 
wall and juice are protective, but if disturbed are attacked either by the 
normally present germs or others to whose entrance in food the dam- 
aged organ offers no resistance. The mechanical conditions mentioned 
in the discussion of bacteria in the stomach play a similar role in the 
intestines. 

Pathological Anatomy. — There are a number of varieties of enteritis, 
and different types may be described, though individual cases rarely 
conform to a single variety. Of the acute forms of enteritis, the impor- 
tant are the catarrhal, suppurative, and the pseudomembranous. 

Catarrhal enteritis may affect any part of the intestinal tract. 
The mucosa is swollen and usually light-red in color; the arteries are 
visibly distended, and not rarely there are petechial hemorrhages. 
The surface is covered with mucous exudate containing desquamated 
and degenerated epithelial cells and emigrated leukocytes; while the 
intestinal contents are rendered liquid by serous exudation. The 
solitary follicles or agminated collections of lymphoid tissue may be 
particularly swollen and cause projections above the surrounding 
mucosa. The term follicular enteritis is applied to such cases (Fig. 277). 
In other instances the desquamation of epithelium is more prominent 
than the mucous exudation, and considerable shreds of mucosa may be 
loosened and discharged. The term croupous enteritis is suggested by 
such conditions. 

The so-called toxic enteritis, such as is seen in toxic (not bacterial) 
meat-poisoning, is of the catarrhal type, with much hyperemia and 
edema. Superficial necrosis or hemorrhage may occur. 



634 



A TEXT-BOOK OF PATHOLOGY 



Suppurative enteritis differs from the catarrhal form in the greater 
degree of emigration of leukocytes. The exudate upon the surface may- 
be largely composed of white corpuscles, and in intense cases the surface 
may be covered with almost pure pus. Round-cell infiltration of the 
mucosa and the submucosa is present, and focal collections leading to 
submucous abscesses or to ulcers upon the mucous surface are occasionally 
seen. The solitary follicles are enlarged and tend to break down, form- 
ing follicular ulcers. 

Pseudomembranous enteritis is characterized by the formation 
of a grayish membrane upon the surface of the intestine. The large 
intestine is more frequently involved, and the process is especially met 
with in dysentery (see p. 639). True diphtheria of the bowel with 
pseudomembranous deposit may sometimes occur. 

The term ulcerative enteritis is sometimes used, but, as a matter of 
fact, non-specific ulcerations are relatively rare. Erosions are commoner. 
It is better to speak of the pathological type of enteritis with ulceration, 




Fig. 277. — Hemorrhagic follicular enteritis. 



as the ulcerative forms are considered under typhoid, tuberculosis, and 
the like. Ulceration of the intestines occurs in a variety of conditions. 
Peptic ulcers, similar to those met with in the stomach (q. v.), are occasion- 
ally found in the duodenum, and are there explained as given for gastric 
round ulcer. They have the same characters and tendencies as those of 
the stomach; they may occasion sudden death from hemorrhage. Ulcers 
in the duodenum are also an occasional result of extensive burns of the 
skin ; and attention has been called to the frequency of duodenal ulcera- 
tion in cases of chronic Bright's disease. Ulcerations of the ileum are 
habitual in typhoid fever and tuberculous enteritis, and are occasionally 
due to anthrax or actinomycosis. Ulcers may be found in all forms of 
enteritis of childhood, especially in intense forms and in cases com- 
plicating the exanthemata. Sarcomata and carcinomata are rare causes. 
Ulcerations of the large bowel are met with in chronic colitis and dys- 
entery. A form of peculiar clinical interest is anal fissure. This is a 
linear ulceration of the rectum in the region of the sphincter. It may 
be associated with hemorrhoids or may be independent. 



DISEASES OF THE GASTROINTESTINAL TRACT 



635 



Chronic enteritis results from acute attacks or from repeated irri- 
tation. Chronic congestion in consequence of hepatic or cardiac affec- 
tions is a predisposing cause of importance. 

In the early stages the mucous membrane is usually more or less 
swollen, and sometimes proliferative changes in the glandular elements 
may lead to distinct polypoid elevations. These are especially pro- 
nounced in cases in which the healing of ulcers of acute enteritis has 
occasioned cicatricial constrictions and thus elevated adjoining parts 
of the mucosa. The elevated portions may undergo proliferative in- 
flammation, and polypoid formations result. In the later stages of 
chronic enteritis atrophy may ensue, in part as the result of the over- 
growth of the stroma of the mucosa and the degeneration of the glandu- 
lar elements, in part also as the result of the overdistention or tympany 
resulting from fermentation of the intestinal contents. This atrophy 
may affect the mucous membrane alone, but more commonly also in- 
volves the muscularis. Hyperplastic processes in the lymphoid ele- 
ments may be a prominent feature in the hypertrophic stage of chronic 
enteritis, and may give place to atrophy in the later stages. On the other 
hand, the enlargement of the solitary follicles and Peyer's patches may 
persist for a long time after atrophy has led to great thinning of the 
remaining portions of the mucosa. 

Pathological Physiology. — Enteritis may occasion profound dis- 
turbances in a variety of ways. In cases of infective character general 
systemic intoxication may result from the absorption of bacterial prod- 
ucts or substances resulting from decomposition of the intestinal con- 
tents. In other cases the intensity of the local irritation may, through 
the nervous system, occasion great depression or shock; and subse- 
quently the exudations into the intestines may cause depletion of the 
vascular system and failure of the circulation. The local effects and the 
resulting behavior of the bowels differ in different cases. Sometimes 
the peristaltic movements are arrested by the intensity of irritation and 
obstinate constipation results; more frequently hurried peristalsis and 
the abnormal exudation (serous or mucous) occasion diarrhea. The 
digestive processes fail from the diseased condition of the bowel, as well 
as from the rapid peristalsis and premature discharge of the intestinal 
contents; more or less profound disturbance of health results. 

INFLAMMATIONS OF SPECIAL PARTS 

Duodenitis occurs in association with gastritis from irritating 
food and the like. The appearances are the same as in gastritis. Du- 
odenitis is prone to occasion obstruction of the terminal portion of the 
common bile-duct by the inflammatory thickening of the mucosa and 
the accumulation of mucus in the mouth of the duct; and in this way 
gives rise to obstructive jaundice (catarrhal jaundice). The inflamma- 
tion may extend into the liver or pancreas along the respective ducts. 

Inflammation of the ileum presents no special characteristics, ex- 
cepting that enlargement of the follicles (follicular enteritis) is fre- 



636 



A TEXT-BOOK OF PATHOLOGY 



quently conspicuous. Follicular ileitis is particularly common in 
children suffering from infectious fevers, such as diphtheria and scarla- 
tina. Peyer's patches may be considerably enlarged and even ulcerated. 
The ulcers are generally small, and several may occur in a single Peyer's 
patch instead of single ulcers, such as occur in typhoid or tuberculous 
enteritis. It is a curious fact that some of the lymph-follicles may be 
free from gross alterations even in severe follicular enteritis. 

Typhlitis or cecitis (inflammation of the cecum) may be due to 
the irritation of the intestinal contents in consequence of constipation 
(stercoral typhlitis). This affection is probably very frequent, though it 
leads to no severe consequences and occasions no urgent symptoms. 
Typhlitis is probably generally of the simple catarrhal variety, but in 
obstinate constipation or obstruction of the colon ulceration may occur. 
Perforation or extension to the surrounding tissues {perityphlitis) is the 
rarest of all consequences. Usually the latter is secondary to inflam- 
mations of the appendix vermiformis. 

Appendicitis may be a primary condition, or it may result from 
primary typhlitis or cecitis. The inflammation of the mucosa of the 
cecum may extend directly to that of the appendix; or may cause ob- 
struction of the mouth of the appendix in the same manner as duodenitis 
causes obstruction of the common bile-duct. There results a retention 
of the contents of the appendix and multiplication with increase in viru- 
lence of the contained bacteria (Bacillus coli communis, staphylococcus, 
streptococcus, and others). The mucosa of the appendix, rendered less 
resistant in consequence of the overdistention and associated congestion, 
may be penetrated by the micro-organisms and appendicitis results. 
There may be some slight defect in the surface epithelium into which the 
bacteria pass. Superficially there is little change, but it is characteristic 
of the appendix that lesions spread into the deep layers to a greater ex- 
tent than on the surface. This deep spread is probably due to early 
if not primary involvement of the lymph tissue, which in swelling ob- 
structs the lumen of the tube and creates recesses within which bac- 
teria multiply. In many cases fecal concretions are found within the 
appendix, and less commonly foreign bodies of various sorts have been 
found. These have been assumed to be the direct cause of the disease, 
and doubtless may play a part by irritating the mucosa, or injuring it in 
such manner that micro-organisms easily penetrate it. On the other 
hand, there is much reason to believe that the fecal concretions are often 
formed in consequence of the accumulation of mucous and desqua- 
mated epithelial cells and the stagnation of the contents of the appendix, 
after the disease has begun. The position of the appendix and rapid 
swelling of its mucosa favor retention of foreign bodies and exudates, 
while its movability renders kinking easy. Typhoid and tuberculous 
ulcers and actinomycosis have been found in the appendix. These 
lesions may occasion secondary appendicitis of an ordinary sort, or they 
may in themselves cause the symptoms of appendicitis. Obstruction 
of the arterial supply of the appendix was formerly regarded as an im- 
portant element in the etiology, but probably is only of secondary im- 



DISEASES OF THE GASTROINTESTINAL TRACT 637 



portance. Appendicitis is less frequent in women than in men. This 
has been ascribed to the existence of a more adequate blood-supply (the 
supplemental part derived from the ovary) in women. 

The pathological anatomy of appendicitis varies in different cases, 
and we may, for convenience, distinguish a catarrhal, a necrotic or gan- 
grenous, and an interstitial form. 

In the mildest or catarrhal form there is merely retention of the 
contents of the appendix and slight disease (swelling and erosion) of the 
mucosa. The muscularis and serous 
coat may be congested and edema- 
tous, but are not extensively in- 
volved. The contents of the ap- 
pendix are more or less mucopuru- 
lent in character, and may, of course, 
become pure pus. 

In the necrotic or gangrenous 
form the mucous membrane suffers 
rapid destruction and the muscular 
and serous coats are quickly in- 
vaded. Fibrinous peritonitis soon 
develops in the serous coat and 
over the adjacent intestines, either 
as a result of penetration of bacteria 
through the walls of the appendix, 
or in consequence of perforation 
of the walls. The local peritonitis 
serves the purpose of restraining the 
infective disease and prevents dif- 
fuse peritonitis. In cases of rapid 
gangrene, with early rupture or es- 
cape of abundant bacteria, general 
peritonitis may result before a re- 
straining wall can be formed. 

The term "interstitial appendi- 
citis" may be used to designate 
cases in which all of the coats of the 
appendix are involved and in which 
there is a special tendency to pro- 
ductive changes in the connective 
tissues. In reality, all cases of ap- 
pendicitis show more or less inter- 
stitial change of this character (Fig. 
278).; but in some it is the con- 
spicuous feature. These cases frequently terminate in chronic thicken- 
ing of the appendix. 

Results. — Mild cases of catarrhal appendicitis may subside after 
free purgation, with relief of the obstruction at the mouth of the ap- 
pendix. In more serious inflammations and in cases in which the ob- 





Fig. 278. — Acute appendicitis, with 
round-cell infiltration and hyperplasia of 
connective tissue in all of the coats. In 
large part the round cells of the mucosa 
and submucosa belong to the normal 
lymphoid tissue of these parts. 



638 



A TEXT-BOOK OF PATHOLOGY 



struction remains, the disease spreads through the walls of the ap- 
pendix to the peritoneum and occasions local peritonitis; or rupture of 
the appendix occurs, and more intense local or general peritonitis fol- 
lows (Figs. 279-281). In either case fibrinous deposits are formed upon 
the peritoneum, and not rarely a localized abscess (periappendiceal abscess) 
results. The appendix itself may be separated from the cecum, and 
may lie free in the abscess, or it may be firmly embedded in the fibrinous 
wall of the abscess. The latter may subsequently undergo inspissation, 
but more commonly ruptures into the general peritoneal cavity, into, 
some part of the intestines, into the ureter, bladder, or externally. In 
cases with favorable outcome the appendix is usually bound down by 
adhesions which attach it to neighboring coils of intestine or to other 
structures. The appendix in such cases is usually distorted and greatly 
thickened, and repeated attacks of inflammation (relapsing or recurring 




Tig. 279-281.— Ulcerative and perforative appendicitis, showing perforations; two fecal 
concretions from other cases of appendicitis (modified from Bollinger). 



appendicitis) are not unusual. Chronic appendicitis may arise in this 
manner, that is, as a remnant from an acute process; but it also occurs 
without involvement of the peritoneum, the lesions being confined to 
the appendiceal mucous and muscular layers. Chronic appendicitis 
may be divided into the catarrhal and sclerosing forms. In the former 
type we have alterations in the structure of the inner coats as the most 
prominent change, while in the sclerotic form connective-tissue over- 
growth occurs throughout all coats, so that finally, by contraction, the 
glandular structures are destroyed, and the organ becomes a fibrous 
cord (obliterating appendicitis). 

There is generally more or less systemic intoxication and infec- 
tion with appendicitis, and degenerative changes and metastatic ab- 
scesses may be found in distant organs. Not rarely pylephlebitis and 
metastatic abscesses of the liver are encountered. 



DISEASES OF THE GASTROINTESTINAL TRACT 



639 



Colitis, aside from the specific form (dysentery), is most frequently 
due to irritation by fecal accumulations, and the sigmoid flexure is the 
common seat. The entire colon may, however, be involved. It may 
assume catarrhal, ulcerative, or pseudomembranous forms, the most 
conspicuous of the last being "mucous colitis." Thickening of the 
mucous membrane and abundant exudation of mucus are the prom- 
inent features of the earlier stages; while in the later stages atrophy 
and thinning are observed. Ulcerations are not uncommon. When the 
mucous exudation and the desquamated cells accumulate upon the 
surface the appearance of a pseudomembrane is simulated, and casts 
of the bowel or masses of mucus may be discharged from time to time. 
The other forms of colitis are in no manner peculiar. 

Proctitis, or inflammation of the rectum, may be due to direct 
irritation by retention of fecal matter, by parasites, or by toxic agents; 
or it may occur secondarily after various other diseases of the rectum, 
such as tumors, hemorrhoids, and the like. The inflammation tends to 
become chronic. The rectum is generally involved with the colon in 
cases of mucous colitis. 

The mucous membrane is considerably swollen, often edematous, 
and usually presents petechial hemorrhages. Ulceration may occur 
secondarily, and extension of the ulcerative process to the surrounding 
tissues (periproctitis) is not unusual. In the latter cases fistulous 
communication may be established between a perirectal abscess and the 
rectum (incomplete fistula), or a fistulous communication may form 
between the rectum and the exterior (complete fistula in ano). Some- 
times proctitis is secondary to periproctitis occurring in diseases such 
as typhoid fever, pyemia, and the like. 

INFECTIOUS DISEASES 

Dysentery is a name applied to two varieties of infectious colitis 
whose etiology is now quite definitely accepted. One form, bacillary 
dysentery, is due to a non-motile bacillus of typhocolon morphology 
(see p. 297), while the other form, amebic dysentery, is caused by a pro- 
tozoon, Entamoeba histolytica (see p. 365). 

Bacillary dysentery is a communicable colitis, presenting acute, 
subacute, or chronic characters, due to one of the varieties of the Bacillus 
dysenteric It appears as epidemics in the tropics, in camps and insti- 
tutions, or may occur sporadically. It seems to be a general infection 
in the acute cases, but there is rarely a bacteremia, except shortly be- 
fore death. The bacteria may at times find their way to the lymph- 
glands draining the affected bowel. Rare instances of septicemia are 
reported. The hygiene and bacteriology have already been discussed. 

The morbid lesions are usually confined to the colon, but may at times 
extend to the ileum. In the large gut the whole length is usually in- 
volved in, at first, a congestive and mucocatarrhal inflammation. This 
is rapidly overshadowed by a superficial necrosis which affects the tips 
of the rugae. Great swelling of the mucosa enlarges and distorts these 



640 



A TEXT-BOOK OF PATHOLOGY 



folds. Over the mucous surface there appears a delicate necrotic film 
which can be rubbed away by the finger, leaving eroded or superficially 
ulcerated surfaces. The mucosa as a whole is swollen, but the process is 
more superficial than in amebic dysentery. In fulminating cases the 
mucosa becomes hemorrhagic or even gangrenous. In subacute and 
chronic cases these changes are not so intense, the follicles being more 
involved and becoming prominent. 

Amebic dysentery is a communicable colitis, usually chronic, but at 
times acute, due to Entamoeba histolytica, endemic in some tropical and 
subtropical countries, occasionally appearing in epidemic or sporadic 
forms in higher latitudes, and showing a great tendency to involve the 
liver with abscess formation. It is commonest among white male adults. 

The lesions are usually confined to the upper colon, although the 
sigmoid and rectum are often involved. When the amebse penetrate the 
mucosa they infest the submucosa, causing great swelling and thicken- 
ing by edema, round-cell infiltration, and proliferation of fixed tissue 
cells. This swelling interferes with the nutrition of the overlying mu- 
cosa, and ulceration is early and extensive; the infiltration is so wide- 
spread and rapid in its extension that intercommunicating swellings, 
and then undermined ulcerations, are produced. The ulcers are of all 
conceivable shapes, and as the infiltration or destruction in the sub- 
mucosa is greater in extent than the loss of surface, mucous membrane 
bridges only may separate the surface's defects. Penetration to the 
muscular or serous coats is known, and perforation is sometimes seen. 
Healing occurs by granulation tissue, beginning around the base of the 
ulcer. 

Microscopically, the infiltrate is of round and tissue cells, and few 
polynuclears are found. Eosinophils are common. The character- 
istics of amebic dysentery are the marked infiltration and thickening 
of the submucosa, in which lie amebse occupying spaces in the cel- 
lular collections, and in lymph- or small blood-vessels. The liver 
lesions consist of single or multiple abscesses or focal necroses with 
parenchymatous degenerations. Abscesses occur chiefly in the right 
lobe near the colonic or diaphragmatic surface. The contents vary 
from serous to a reddish-brown, puriform, necrotic material, in which, 
near the wall, amebae may be found. This wall consists of a layer 
of dense tissue cell proliferation and infiltration of round cells, with 
great congestion about it. These abscesses may rupture, the com- 
monest direction being through the diaphragm to pleura and lung. 

Cholera. — Cholera epidemica or Asiatica is an acute specific 
inflammation of the small and large intestines due to the comma 
bacillus or vibrio of Koch. This micro-organism is found in the 
great majority of cases, but occasionally it is not discovered, while other 
micro-organisms, Bacillus coli communis and streptococci, are present. 
It is probable that in these instances errors of observation cause the 
failure of detection. 

Pathological Anatomy. — Cholera is characterized by redness and 
swelling, and not rarely by petechial ecchymosis of the mucous mem- 



DISEASES OF THE GASTROINTESTINAL TRACT 



641 



brane, particularly of the small intestine (ileum). The superficial epi- 
thelium suffers early an extensive degeneration, perhaps a form of 
coagulation necrosis. The solitary follicles and the agminated glands 
may enlarge and may suffer ulceration. The intestines contain and 
discharge a serous exudation, often in large quantities, in which are 
grayish or whitish particles, consisting of flakes of desquamated and 




Fig. 282. — Typhus abdominalis: medullary Fig. 283. — Typhus abdominalis: ulcers 
swelling. with slough removed. 

degenerated epithelium. The term "rice-water discharges" is applied 
to the evacuations. Extensive areas of the mucous membrane may be 
laid bare by the desquamation of the epithelium. When cholera has 
passed to its later stages, secondary pseudomembranous inflammation 
of the mucous membrane is not unusual, and is probably the result of 
secondary infection. 

41 



642 



A TEXT-BOOK OF PATHOLOGY 



Associated Conditions. — The blood is thickened and dark red in 
color; thrombosis in the heart or venous sinuses is frequent. These 
are due to the great loss of water by the diarrhea. The kidneys present 
marked congestion and degeneration, which are dependent upon the 
action of the toxins of the disease. Lobular pneumonia is a common 
complication. There is apt to be a slight fibrinous peritonitis, while 
the gut itself is thin and atrophic. 




Fig. 284. — Typhus abdominalis: superficial necrosis. 



Typhoid fever is distinguished by an acute, specific inflammation 
of the lymphoid elements of the intestines, particularly of the ileum and 
upper portion of the colon (Figs. 282-285). The specific cause is the 
Bacillus typhi abdominalis, described by Eberth and Gaffky. This or- 
ganism enters the gastro-intestinal tract with drinking-water, milk, or 
other food, and multiplies in the small intestine (see page 289). 



DISEASES OP THE GASTROINTESTINAL TRACT 



643 



Pathological Anatomy— The specific lesions of typhoid fever occur 
in the lymphatic structures, notably in the solitary follicles, Peyer's 
patches, mesenteric glands, and spleen. It is, however, wise to remem- 
ber that a few cases of typhoid bacillus infection giving a Widal reaction, 
but without intestinal lymph-gland ulcers, have been observed, or with 
only small atypical mucous membrane lesions. The bacteremia and 
parenchymatous lesions may be otherwise as typically described. 

The solitary follicles and Peyer's patches of the lower end of the 
ileum are first affected, but later, or exceptionally in the beginning, the 
lymphoid collections of the upper part of the ileum and jejunum, or of 
the cecum and colon, may be involved. At first the follicles and patches 
are swollen and somewhat reddened by congestion. Within a few days 
of the onset, however, they lose their congested appearance and pre- 
sent themselves as grayish or white elevations projecting from one 
to several millimeters above the surface (Fig. 282). Microscopically, 
the lymphoid elements are found in a state of active proliferation, and^ 




Fig. 285. — Typhoid fever, showing necrosis of Peyer's patches and intense congestion of 
the bowel (modified from Kast and Rumpel). 

in addition, large round cells (endothelioid) are more or less abundant. 
These large cells are actively phagocytic, and have been discovered 
in the lymphatic channels at some distance from the local lesions, as 
well as in the mesenteric glands and in distant parts. These cells in- 
crease in number, and may in some areas outnumber the small round cells. 
The surrounding mucosa may be normal in appearance or may be some- 
what inflamed. The dense cellular packing gives a pale color to this 
stage of medullary infiltration, which remains unchanged for some days 
or a week. After the first week necrosis is prone to occur. The center 
of the solitary follicles or part of the Peyer's patch becomes more and 
more soft and yellow, or sometimes reddish from absorption of blood- 
pigment. The necrotic portions are discharged after a few days, leaving 
an ulcerated surface of regular or irregular outline, and presenting over- 
hanging necrotic edges with hemorrhagic infiltration (Figs. 284-287). 
Sometimes not all of the swollen glands slough away, and a knobby or 
granular appearance results from the retention of isolated lymph-follicles. 



644 



A TEXT-BOOK OF PATHOLOGY 



The ulcers resulting from destruction of the solitary follicles are 
small and rounded, while those involving the Peyer's patches are elon- 




Fig. 286. — Typhoid fever. Swelling of lymph-follieles, cross-section of Peyer's patch 

(Karg and Schmorl). 



gated, the long axis being parallel with the axis of the intestine. The 
bases are smooth except, perhaps, for muscular ridging. The ulcers 




Fig. 287. — Typhoid fever, slough formation, showing edge of Peyer s patch becoming 
necrotic. The mucosa to the right shows catarrhal inflammation which usually accom- 
panies the follicular lesions (Karg and Schmorl). 

are usually found in an acute stage at the end of the second or at the 
beginning of the third week of the disease. Resolution may occur with- 
out necrosis and ulceration, but more commonly ulcers are formed and 



DISEASES OF THE GASTROINTESTINAL TRACT 



645 



healing proceeds more slowly. The lymphoid elements of the follicles 
and patches are usually permanently destroyed, and healing takes 
place by proliferation of the fibrous stroma. A covering for the bared 
muscle is made from the mucosa after the inflammatory swelling has 
left the edges of the ulcer. Occasionally, however, complete restitu- 
tion of the normal tissues occurs. When the lymphoid follicles of the 
patches have become necrotic and have been infiltrated with blood, 
dark pigmented spots are formed, and give rise to the condition desig- 
nated as the "shaven-beard" appearance. 

Complications. — Extensive necrosis may lead to erosion of a blood- 
vessel and hemorrhage; or the wall of the intestine may be completely 
perforated by the necrotic process, and fatal peritonitis may result. 
In other instances peritonitis occurs without perforation by direct 
extension of the inflammatory process through the intestinal wall. 
Very commonly slight reactive peritonitis is found on the serous surface 
opposite the ulcers. Extensive peritonitis rarely occurs in this way. 
Peritonitis in rare instances results from necrosis of the mesentery 
glands, or from rupture of the spleen. 

The mesenteric glands are characteristically enlarged, those nearest 
the points of ulceration being first and most prominently involved. 
In the first stage they are soft and dark red in color, exuding a small 
amount of liquid on section. Later, they become larger, harder, and of 
whitish appearance; they may finally suffer necrosis and rupture. 
Usually, however, resolution takes place after the first stage. 

The spleen is enlarged in most cases, and presents the characteristics 
of acute splenic tumor. Very rarely perisplenitis or abscess may occur. 
In the bone-marrow there is an increase of the small round cells and 
large phagocytic endothelial cells. 

The typhoid bacillus seems to have the power to stimulate the endo- 
thelial cells, for we now look upon the large cells of the lesions in Peyer's 
patches as endothelial, and certain it is that these cells, in lymph-glands, 
spleen, and bone-marrow, are found in great abundance. They are 
phagocytic for necrotic cells and bacilli. 

Lesions in Other Parts. — The muscles, particularly those of the 
abdominal walls, frequently show spots of degeneration of a waxy or 
hyaline character, as described by Zenker. Very rarely petechial or 
considerable hemorrhages may be found in the muscles; and abscesses 
are sometimes met with as sequelae. 

The heart muscle is involved in perhaps a majority of the cases. 
The muscle-fibers suffer parenchymatous and hyaline degeneration, and 
less commonly the intermuscular tissues present the characteristics of 
acute myocarditis. Acute endocarditis and inflammations of other 
serous surfaces are rare in typhoid fever as compared with some other 
infectious diseases. 

Acute degeneration of the kidney and acute nephritis are quite 
common, and the kidney substance may present small lymphomatous 
foci. Similar lymphomata occur in the liver and throughout the peri- 
toneum. Small necrotic foci are also found in the kidney and liver. 



646 



A TEXT-BOOK OF PATHOLOGY 



Acute lobular pneumonia and croupous pneumonia are frequent 
complications. Osteomyelitis is rare. 

The blood in typhoid fever, unlike other infections, presents no 
leukocytosis, but, on the contrary, usually shows a leukopenia, the 
mononuclear leukocytes predominating. 

Cholecystitis and gall-stones have been traced to typhoid fever. 
Thrombosis, particularly of the veins, has been known, and more lasting 
alterations in arteries, Thayer believes, may be caused by the typhoid 
bacillus. 

Paratyphoid Fever. — This infection occasions variable lesions in 
the intestines. There may be simple or follicular enteritis, or ulceration 
of the lymph-nodes has been seen. The systemic condition is more of a 
bacteremia without definite localizing manifestations. It is to' be 
differentiated from typhoid by bacteriological tests. 

Tuberculosis of the intestines may be primary or secondary. It 
may, in rare cases, occur primarily from the drinking of infected milk 




Fig. 288. — Tuberculous ulceration of the intestine. 



or consumption of the meat of tuberculous animals. Primary tuber- 
culosis of this character is most often seen in young infants. More 
commonly tuberculosis of the intestines is secondary to pulmonary or 
laryngeal tuberculosis, and is due to the swallowing of sputa. 

In following the course of the tubercle bacillus in its production of 
intestinal tuberculosis one must remember that this organism can 
pass the undamaged mucosa without leaving a trace. It may settle in 
a submucous lymphatic, or be carried to a mesenteric gland. In the 
former case the primary lesion is a submucous tubercle which can extend 
(a) along the transverse lymphatic vessels, (b) through the muscularis 
to a position under the serosa, and (c) toward the mesenteric insertion 
and to the mesenteric gland. If no lesions occur in the gut wall, but 
begin in the mesenteric glands, then the lesion may extend toward the 
gut along the mesentery, and break out as subperitoneal tubercles 
which have the power to penetrate along the lymphatic vessels com- 



PLATE ii 




Tuberculous ulceration in intestine showing miliary and infiltrative lesions beneath 
peritoneum and in mesentery. 



DISEASES OF THE GASTROINTESTINAL TRACT 



647 



municating between the submucosa and peritoneum. Tuberculous 
peritonitis, which usually assumes a plastic nature, may arise this way. 

The usual situation of the lesions is the lower end of the ileum, 
and it is the lymphoid tissues that are prone to be attacked. At first 
the follicles or Peyer's patches become enlarged and project above the 
surface. Soon they undergo necrosis and discharge their contents, 
leaving more or less irregular caseous ulcers. The follicular ulcers are 
small and rounded, but the more characteristic lesion is an irregular 
ulcer extending transversely to the long axis of the bowel and often 
involving one-half or more of the entire circumference (Fig. 288). 

Microscopically, the changes are found to involve the mucous mem- 
brane and the adjacent submucous coat. Early caseation is charac- 
teristic. On the serous coat may often be seen granular elevations in 
clusters opposite the ulcers in the mucosa, and extending in lines from 
the region of ulceration around the bowel toward the mesentery (Fig. 




Fig. 289. — Miliary tubercles in clusters and disseminated over the serosa (peritoneum) 
of the intestine; the clusters are situated opposite ulcerations of the mucous membrane 
(modified from Bollinger). 

289). These represent tuberculous lymphangitis and small miliary 
tubercles in the course of the subserous lymphatic vessels. 

Tuberculous ulceration rarely causes perforation of the bowel, ex- 
cepting in the rectum, where periproctitis and fistula in ano may result. 
The ulcers may heal, causing cicatricial distortion or stenosis. Very 
commonly there is associated tuberculous enlargement of the mesenteric 
glands, and sometimes the latter are extensively diseased, though the 
primary intestinal involvement is insignificant. Generalized enteritis 
of catarrhal character may accompany the specific ulcerative disease. 

There can be hematogenous miliary tuberculosis of the gut arising 
as a part of the general form, as peritoneal, subperitoneal, submucosal, 
or interstitial tubercles. 

Occasionally a hyperplastic intestinal tuberculosis occurs in which 
the productive tissue growth exceeds the caseation. 

Syphilis is most frequent in the rectum, though cases of syph- 
ilitic disease of the small intestine or colon, in the form of localized 



648 



A TEXT-BOOK OF PATHOLOGY 



or diffuse gummatous involvement, sometimes with secondary ulcera- 
tion, have been observed, particularly in cases of congenital syphilis. 

In the rectum syphilis may appear in the form of warty eleva- 
tions or as a chancre; also as mucous patches, gummatous nodules, or 
infiltrations. Considerable thickening of the mucosa and submucosa, 
with ulceration and secondary cicatrization and stenosis {syphilitic 
stricture), may result. 

Anthrax occasionally affects the small intestine in persons exposed 
to infection by their occupations. It is met with among wool-sorters, 
brushmakers, tanners, and the like. More or less extensive ulceration 
is seen in the small intestine, and sometimes in the large intestine. 
The ulcers are dark colored and necrotic in appearance, and are com- 
monly surrounded by a hemorrhagic zone. Considerable edema and 
hemorrhagic infiltration of the neighboring parts of the intestine may 
accompany the ulceration. The neighboring lymph-glands and the 
spleen are enlarged. The bacilli of anthrax are found in considerable 
numbers in the ulcers and in the surrounding tissues. 

Actinomycosis of the intestines is very rare. It most commonly 
affects the region of the cecum, causing first infiltrations, and then 
ulcerations of the mucosa and submucosa. 

Enteromycosis is a term applied to intestinal affections resulting 
from the ingestion of putrid meat, fish, sausages, and the like. Occa- 
sionally considerable epidemics may occur. The intestines may present 
the lesions of catarrhal enteritis or of intense croupous or pseudomem- 
branous inflammation, and there may be erosions or ulceration. Micro- 
organisms of various sorts have been discovered, but no specific form is 
recognized. The acute general symptoms, and even the local lesions, 
may be caused by poisons elaborated by bacteria in tainted foods 
rather than by the micro-organisms themselves. 

TUMORS 

Connective=tissue Tumors. — Among the benign tumors of the 

intestines, fibroma, myxoma, and lipoma are occasionally met with in 
the submucosa as small nodular tumors or as pendulous polyps. They 
may occasion intestinal obstruction and even invagination. 

Sarcoma of the intestine is rare. Lymphosarcomatous or lymph- 
adenomatous enlargement of the solitary follicles or Peyer's patches 
may be met with in leukemia or pseudoleukemia. Round-celled sarcoma 
springing from the submucosa and deeper layers of the mucosa, and 
sometimes infiltrating the mesentery, may also occur as an independent 
and primary affection. Nodules of secondary sarcoma are not rarely 
met with in the mucosa and submucosa of the intestines (Fig. 290), and 
the serous covering may be studded with miliary nodules in sarcomatosis. 

Epithelial Tumors. — Among the epithelial tumors may be included 
inflammatory papilloma, adenoma, and carcinoma. 

Inflammatory hyperplasia of the mucous membrane may occur 
in association with chronic inflammations, especially in the large intes- 



DISEASES OF THE GASTROINTESTINAL TRACT 



649 



tine, and may lead to the formation of papillomatous or polypoid eleva- 
tions of considerable magnitude. 

Adenomata are more strictly of the nature of tumors, being inde- 
pendent of inflammatory processes, although no sharp dividing-line 
can be drawn between the inflammatory proliferations and the adeno- 
mata proper. The latter may occur in the form of flat elevations hav- 
ing a more or less uneven surface and a tendency to hemorrhage and 
ulceration; or in the form of papillomatous elevations of a cauliflower 
character. Adenomata arise by hyperplasia of the crypts of Lieberkuhn 
in the duodenum, or of Midler's glands, and in their structure they pre- 
sent typical glandular acini, the tubules having a basement-membrane 
lined with cylindrical epithelium. Adenomata are most frequent in the 




Fig. 290. — Nodule of secondary sarcoma in the mucosa of the intestine (Kast and Rumpel). 

rectum, but may occur in other parts of the large intestine and in the 
duodenum. 

Carcinoma is the most frequent tumor of the intestines. It occurs 
in the duodenum, especially at the papilla of the common bile-duct 
(Fig. 291) ; at the ileocecal valve, at the flexures of the colon, and in the 
upper or lower part of the rectum. The appearance is that of a soft, 
irregular, often ulcerated and bleeding elevation, projecting into the 
lumen of the gut and causing considerable narrowing, or surrounding 
the bowel by circular involvement of the entire circumference. The car- 
cinomata of the bowel are, for the most part, cylindrical epitheliomata 
(Fig. 292) or glandular cancers, consisting of atypical acini and tubules, 
with irregular proliferation and infiltration of the neighboring tissues 



A TEXT-BOOK OF PATHOLOGY 




Fig. 292. — Cylindrical epithelioma of the intestine (Perls). 



DISEASES OF THE GASTROINTESTINAL TRACT 



651 



with masses of epithelial cells. Cases are met with, especially in the 
rectum, in which there is a clear transition of adenoma into carcinoma 
(adenocarcinoma), and, in general, adenomata of the bowel have a 
tendency to such transformation (Fig. 293). At the lower end of the 
rectum squamous epithelioma may occur. 

The results of carcinoma of the bowel are the same as those of stenosis 
due to other causes, together with the consequences of the cancerous 
cachexia and of metastasis. Ulceration of the tumor may lead to per- 
foration. Metastasis occurring to liver and other structures in the 
peritoneum is not uncommon. Outside of this cavity the secondary 
growths are rare. Secondary growths in the intestine are not so common. 




Fig. 293. — Adenocarcinoma of the rectum (adenoma destruens) (Karg and Schmorl). 

They come from growths in the stomach and uterus especially. Car- 
cinomata of the appendix are more common than previously supposed. 
They are of the scirrhous or simple variety and seldom cause symp- 
toms or metastases. 

Myoma of the intestines and multiple cysts are occasionally met 
with. 

PARASITES 

Vegetable Parasites. — Various forms of bacteria are found with 
such frequency in the intestinal contents that it is difficult to estimate 
their pathological significance. Tubercle bacilli, the bacillus of glanders 
and of typhoid fever, and the Streptothrix actinomyces produce the 
specific lesions of these diseases. The Bacillus coli communis is a con- 



652 



A TEXT-BOOK OF PATHOLOGY 



stant inhabitant, but probably assumes pathogenic properties and 
leads to inflammatory lesions when the conditions (such as irritation 
by coarse food, congestion, obstruction) favor its activity and multi- 
plication. Under the same circumstances other micro-organisms like- 
wise become active in the production of enteritis. 

Animal Parasites. — The animal parasites are discussed in detail 
elsewhere, but may be briefly mentioned here with reference to patho- 
logical results occasioned by their presence. Various forms of protozoa 
have been found, and may occasion inflammation when in considerable 
numbers. Coccidial psorospermia occur in the epithelium of the villi 
of the small intestine, and the Lamblia intestinalis may be found at- 
tached to the epithelium. The dysentery amebse may lie free in the 
contents, or may be found in the tissues, especially in the vicinity of 
ulcerations. They inhabit the large intestine, and are the cause of 
a certain kind of dysentery. 

The larger intestinal parasites are, for the most part, species of 
Vermes. Among the tapeworms, Tcenia saginata, T. solium, and Di- 
bothriocephalus latus are the most frequent. Occasionally these may 
lead to intestinal obstruction by forming thick knots or coils, and some- 
times the head of the worm may be attached in the mouth of the bile- 
duct, causing obstruction and jaundice. Inflammatory changes are 
rarely met with as a result of these worms. 

Among the nematodes, or round-worms, the Ascaris lumbricoides, 
or ordinary round-worm, is the most frequent. It is usually multiple, 
and may occasion obstruction of the intestine or inflammation. Some- 
times it perforates the intestinal wall, but it is improbable that the 
perforation is due entirely to the action of the worm. Previous intes- 
tinal ulceration is the more important condition. Obstruction of the 
bile-ducts or of the appendix may occasionally be due to lumbricoids. 
The Ankylostomum duodenale may cause petechial hemorrhages and in- 
flammatory disturbances in the duodenum or jejunum. The worms 
attach themselves firmly to the mucous surface and may be present in 
large numbers. The O.ryvris vermicularis, or thread-worm, occupies the 
large bowel, multiplying in the cecum and descending in the mature 
state to the rectum; it may occasion considerable proctitis. In female 
children vaginitis sometimes results from migration of the worms. 
The Trichinella spiralis when ingested in large numbers occasions violent 
gastro-enteritis, and its embryos perforate the wall of the intestine and 
migrate to the muscles. 

Larva? of various forms of flies occasionally occupy the intestinal 
tract, and owe their presence to the ingestion of the eggs with food. 
They may occasion enteritis, and may be found in immense numbers 
in the bowel or the stools. 

INTESTINAL RUPTURE AND FOREIGN BODIES 

Rupture may be due directly to traumatism or penetrating wounds;; 
but more frequently results from ulcerations within. Duodenal (peptic) 



DISEASES OF THE GASTROINTESTINAL TRACT 



653 



ulcers not infrequently perforate, and typhoid ulcers occasionally cause 
rupture. Tuberculous, dysenteric, and other ulcers are less prone to 
penetrate completely. The appendix may rupture from obstruction 
at its mouth and secondary catarrhal, necrotic, or gangrenous inflam- 
mation of its walls. Rectal ulcers frequently cause painful diarrhea, 
proctitis, periproctitis, and fistuke. 

Intestinal rupture usually leads to rapid peritonitis, but occasionally 
recovery ensues. A localized peritonitis, by walling off the infected 
area, may prevent general infection. The rupture may take place 
between adherent coils, causing spontaneous intestinal anastomosis. 

Foreign Bodies. — Various bodies that have been swallowed may 
lodge in the intestines. Occasionally fecal concretions or enteroliths 
are found, especially in the appendix. These consist of a nucleus of 
epithelial cells, mucus, hair, and the like, surrounded by inspissated 
fecal matter and earthy salts, particularly phosphate of lime and car- 
bonate of calcium. They may cause considerable irritation, especially 
in the appendix, and even perforation. 

Intestinal sand is a collection of fine particles of inorganic matter 
with a little organic matter. Certain foods, like bananas, favor its de- 
velopment. 

The Liver 

Anatomical Considerations. — The liver is peculiar in having a 
double circulation: one system of vessels, the portal vein and its ultimate 
subdivisions, receiving the blood from the digestive tract for functional 
purposes; the other system, the hepatic artery and its branches, sup- 
plying the nutritive blood for the walls of the blood-vessels and for the 
interlobular connective tissues, as well as to a certain extent the proper 
hepatic structure itself. The portal capillaries ramify through the acini 
and empty into small branches of the hepatic vein lying in the center 
of the acini. The capillaries of the hepatic artery traverse the inter- 
lobular tissue and ultimately empty into the interlobular branches of 
the hepatic vein. The primary biliary capillaries are merely spaces 
between the hepatic cells, the larger formed capillaries occupying the 
interlobular tissues. 

MALFORMATIONS AND CHANGES OF POSITION 

Congenital malformations are uncommon. There may be complete 
absence of the organ, especially in certain monstrosities; more frequently 
adventitious hepatic tissue is found in the suspensory ligament or else- 
where. Minor abnormalities in the lobes or fissures are more frequent. 
Absence of the gall-bladder and congenital stenosis or occlusion of the hepatic 
ducts are occasionally met with. 

Congenital Alterations of Position. — The liver may occupy the 
left side in transposition of the viscera. More rarely it is displaced 
downward or occupies other abnormal positions. 

Acquired Changes of Form. — The most important of these is con- 
traction and lengthening of the organ by lacing. This gives rise to com- 



654 



A TEXT-BOOK OF PATHOLOGY 



pression along the line of the lower margin of the ribs; the right lobe of 
the liver may thus be divided into an upper and a lower portion by a deep 
fissure. The capsule is frequently thickened and the superficial acini 
atrophic at the line of constriction (Fig. 294). Similar indentation by 
the ribs posteriorly, or by the right crus of the diaphragm, results from 
pulmonary affections and enlargements of the liver. Other changes of 
form, due to special diseases of the liver, will be discussed below. 

Acquired Changes of Position. — Downward displacement may 
result from pleural effusion or emphysema; or it may be due to relaxa- 
tion and lengthening of the suspensory ligaments. The latter form is 




Fig. 294. — Corset liver (from a specimen in the collection of Dr. Allen J. Smith). 



more common in women than in men, and is often part of a general 
visceroptosis. Tight lacing may be a cause of importance. Displace- 
ment to the right or left, or tilting upward of the lower edge, may occur 
in association with various abdominal and thoracic affections. 

CIRCULATORY DISTURBANCES 

Anemia of the liver may be part of a general anemia, or it may be 
due to pressure upon the organ, to various diseases of the liver substance, 
or to compression of the blood-vessels. The substance becomes pale and, 
if the anemia persists, undergoes degeneration. 

Active hyperemia is physiological during digestion, and occurs in 
association with various inflammatory abdominal diseases. It is rarely 
extensive, and does not lead to marked pathological changes. 

Passive hyperemia results from obstruction to the circulation due 
to cardiac or pulmonary diseases, to pleural effusion or adhesions, or to 
thrombosis or compression of the upper part of the inferior vena cava. 



DISEASES OF THE GASTROINTESTINAL TRACT 



655 



It is especially characteristic of cardiac affections, the sluggish venous 
circulation of the liver accounting for the fact that this organ first evi- 
dences failing cardiac power. 

The liver increases in size, often considerably; the edges are rounded, 
and the color on the surface is darker than normal. On section, there may 
be seen deeply congested central veins surrounded by lighter areas, repre- 
senting the substance of the acini. If the process has persisted, secondary 
fatty degeneration of the peripheral zones of the acini or atrophy of 
these takes place, and the light color of such portions, contrasting 
strongly with the dark, congested central vein, suggests the name 




Fig. 295. — Nutmeg-liver: chronic congestion due to cardiac disease (Bollinger). 

nutmeg-liver (Fig. 295). In some instances of intense congestion small 
hemorrhages may occur, especially in the portions lying beneath the 
capsule. In the later stages degeneration and reduction of size may 
take place and the organ may become dark red from deposit of hema- 
togenous pigment. To this form the term red atrophy is sometimes given. 
In other instances hyperplasia of the connective tissues between the 
lobules and acini occurs, while at the same time the organ is darkly 
pigmented. The term cyanotic induration may appropriately be given 
to such. Cases of this sort are, in reality, instances of secondary cirrhosis. 

Passive congestion of the liver may occasion considerable disturb- 
ance of the hepatic function. The most striking evidence of this is 



656 



A TEXT-BOOK OF PATHOLOGY 



jaundice. This is probably due to the compression of the smaller 
biliary ducts and capillaries, and in part to swelling of the lining cells 
of these channels. The bile at the same time is probably thicker than 
normal, and does not, therefore, as readily escape through the ducts as 
in health. Microscopically, one sees fatty degeneration of the liver- 
cells with pigmentation within and between them, and large liver-cells 
with large or reduplicated nuclei as evidences of attempt at repair. 
The capillaries are distended with blood, the liver columns separated, 
and probably hemorrhagic necroses about the central veins occur, 
although a chronic passive congestion may exist for some time without 
necroses. Oertel describes a general acute necrosis of the liver due to 
hyperemia associated with jaundice and intoxication. The necrosis 
begins in the center of the acini, outside of which soon appear a fat in- 
filtration and bile-pigment deposit. There is no stagnation of bile in 
the capillaries between the lobules. 




Fig. 296. — Coagulation necrosis of the hepatic cells in a case of puerperal eclampsia (Karg 

and Schmorl). 

Embolism and thrombosis of the portal vein may occur in con- 
sequence of various diseases of the gastro-intestinal tract, particularly 
in cases of ulcerative enteritis. Embolic occlusion of one of the larger 
branches of the portal vein may occasion no serious circulatory dis- 
turbances on account of the free collateral circulation, and from the 
fact that the hepatic artery is capable of supplying the entire hepatic 
circulation. Embolic or thrombotic occlusion of the branches of the 
hepatic artery is similarly devoid of serious disturbance of the circula- 
tion, although a wedge-shaped hemorrhagic infarct, like a lung infarct, 
arises ; but no degeneration is apt to follow unless the portal system for 
the same liver section is also damaged. 

Obstruction of the interlobular branches of the portal vein, and 
particularly when several are coincidently occluded, may occasion 
decided nutritive disturbances in the hepatic acini. Small areas of 
necrosis having a grayish or yellowish and somewhat granular appear- 
ance, or in other cases foci of necrosis with hemorrhagic infiltration, are 
the striking lesions. Such conditions are observed in most instances of 
death from puerperal eclampsia in consequence of toxemic thrombosis 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



657 



or of embolism of placental cells (Fig. 296), and in consequence of 
various intoxications or infections having their origin in the distribution 
of the portal circulation. The immediate cause of the lesions in the 
latter condition is hyaline thrombosis of the interlobular portal vessels. 

Thrombosis of the portal vein is most frequently the result of in- 
fective inflammation of the vein (pylephlebitis), resulting from ulcera- 
tive enteritis, appendicitis, or similar processes involving the parts from 
which the portal blood is received. There may be a gradual ascending 
inflammation and thrombosis extending from the primary focus of 
disease to the portal vein ; or the latter may be involved in a more direct 
manner by infectious embolism. The portal vein and its branches in 
the liver become more or less obstructed, and serious disease of the liver 
may occur (multiple abscesses). At the same time the obstruction of 
the vein occasions intense passive hyperemia of the peritoneum, and 
ascites results. 

ATROPHY AND DEGENERATIONS 

Atrophy of the liver occurs in cases of death from senility, inani- 
tion, or from various organic diseases. (Pressure-atrophy has been 
referred to above. Acute yellow atrophy is described below.) 

The greater part of the liver structure may be affected, or the 
atrophy may be confined to the edges or other limited portions. The 
liver is more or less uneven, and may at the same time be somewhat 
pigmented. Microscopically, the liver-cells are decreased in size, gran- 
ular, and dark colored. At times the acini may disappear entirely, 
and reactive hyperplasia of the stroma and even proliferation of biliary 
ducts may ensue. 

Localized atrophy occurs in the vicinity of tumors, in the acini 
surrounded by hyperplastic connective tissue in cirrhosis, and in parts 
of the liver otherwise subjected to pressure. The liver-cells of the 
affected part become distorted and decreased in size, and are deeply 
pigmented (see Fig. 312). In the later stages they break down com- 
pletely and are removed. Red atrophy (see Congestion of the Liver) is 
a form of pressure-atrophy with pigmentation, the compression of the 
hepatic cells being due to overdistention of the hepatic veins and capil- 
laries. 

Pigmentation of the liver is prone to occur on account of the slug- 
gish circulation through that organ, and may be of various kinds: 

1. Hematogenous pigmentation (hemachromatosis) in the portal 
areas. Particles of altered blood-pigment are often deposited in the 
interlobular tissues, especially in Kupffer's stellate cells, or in the periph- 
eral zones of the acini in cases of abnormal blood obstruction in the 
portal circulation. This is particularly common in pernicious anemia. 
In this disease the peripheral zones of the acini are habitually infil- 
trated with pigment matter, which responds to tests" for iron, such as 
with ammonium sulphid or ferrocyanid of potassium and hydrochloric 
acid. Somewhat similar pigmentation of the liver may occur in cases 
of absorption of hemorrhagic effusions in the peritoneum, or in conse- 

42 



658 



A TEXT-BOOK OF PATHOLOGY 



quence of other forms of blood destruction. Analogous pigmentation is 
often met with in the livers and other abdominal organs of drunkards. 
In the slate-colored liver of chronic malaria pigment is found along 
sinusoids, especially in Kupft'er's cells. This is thought to come from the 
destroyed plasmodia and from disintegrated red blood-cells. 

2. Hematogenous pigmentation of the central portions of the acini 
has been noted in connection with a red atrophy of the liver conse- 
quent upon congestion. 

3. Biliary pigmentation results from obstruction of the biliary ducts, 
and is constantly met with in certain forms of cirrhosis and in the 
vicinity of new growths which compress the biliary passages. In 
jaundice, bile-pigments are found within liver-cells and in the supporting 
tissue. 

4. Very rarely anthracotic pigmentation has been observed. In 
one case, at least, there was associated cirrhosis. 




Fig. 297. — Fatty infiltration of the liver. 



Fatty infiltration is more or less physiological, especially in children 
and in overfed individuals. Pathologically, there may be diffuse in- 
filtration or deposit in the liver-cells of all parts of the organ. Such 
pathological fatty liver may result from overeating and general obesity, 
or may be due to pulmonary disease or anemic and cachectic conditions. 
It has generally been held that the immediate cause is retarded oxidation, 
in consequence of which fat accumulates. It is probable, however, that 
there is some disease of the hepatic cells, rendering them more active in 
storing, or less active in disposing of, fats. This seems especially true 
in certain cases due to poisons which cause a deposit of fat in the 
liver, as in geese pampered by antimonial poisoning. 

The liver increases in size, often considerably; its edges are rounded, 
its consistency is doughy, and the color is rather yellowish and glisten- 
ing. On section, there may be visible exudation of oil-drops and the 
knife may be covered with droplets. 

Microscopically, the process is found to begin in the peripheral 



DISEASES OF THE GASTROINTESTINAL TRACT 



659 



portions of the acini in the form of droplets within the hepatic cells. 
Soon these increase in size by confluence, adjacent cells are involved, 
and the entire acinus eventually becomes affected (Fig. 297). In ex- 
treme cases the hepatic cell is filled with a single large oil-drop, which 
compresses the protoplasm and nucleus. The blood-vessels and other 
structures may be completely hidden from view; and the pressure of the 
fatty deposit may be sufficient to produce a certain degree of anemia, 
though not enough to occasion serious circulatory disturbances. The 
functional activity of the liver is diminished. 

Parenchymatous degeneration, or cloudy swelling, occurs in various 
infectious fevers and in consequence of intoxications, notably by phos- 
phorus, arsenic, and antimony. The liver is somewhat enlarged, and of 
an opaque, grayish-yellow appearance, the outlines of the lobules being 
extinguished. Microscopically, the liver-cells are found filled with- fine 
albuminous granules more or less obscuring the nucleus. In most in- 
stances cloudy swelling terminates by return to the normal state ; but if 
the intoxication or infection is continued, fatty degeneration may result. 

Fatty degeneration may occur as the result of severe anemia, par- 
ticularly pernicious anemia, or following cloudy swelling, as the result 
of infectious diseases or of intoxications. Among the infections, pyemia, 
yellow fever, relapsing fever, and erysipelas are notable examples. 
The liver may be greatly decreased in size and softer than normal; the 
substance not rarely is friable. The color is yellowish and oil-drops 
may exude from the surface. Microscopically, the hepatic cells are 
filled with small granular particles or droplets of fat, and in the advanced 
stages they break down completely into granular detritus. The nucleus 
is not pushed aside, but may show fragmentation of the chromatin. 
The liver-cells may contain single large drops of fat practically indis- 
tinguishable from those seen in fatty infiltration. The distinction of the 
two conditions may be exceedingly difficult. Fatty degeneration of local- 
ized areas of the liver or of individual acini or cells occurs in association 
with chronic hepatitis or other diseases causing pressure upon the acini. 

Acute Yellow Atrophy. — The most advanced fatty degeneration 
of the liver occurs in the affection of the organ termed acute yellow 
atrophy. This condition is most frequent in young women, and espe- 
cially in those addicted to the excessive use of alcohol. Occasionally 
syphilis seems the etiological factor, and in acute phosphorus- and 
late chloroform-poisoning the appearance of the liver is the same as that 
which is recognized as acute yellow atrophy. Whipple's work would 
indicate that chloroform destroys the fat-splitting ferment of liver-cells. 
Finally, some cases are idiopathic, arising without recognizable cause, 
which are now attributed to autogenous poisons from the intestinal or 
genital tract. Parturition seems a determining cause in some cases. 
Micro-organisms of various kinds have been found, and it is likely that 
all cases are toxic or infectious. 

Pathological Anatomy. — The liver is decreased in size and becomes 
remarkably soft and friable. On section, there is found a variegated 
appearance, the prevailing color being a brownish or grayish yellow, 



660 



A TEXT-BOOK OF PATHOLOGY 



in which are scattered bright or dark red areas. The yellowish areas 
represent the degenerated and pigmented hepatic cells; the reddish areas, 
foci of hemorrhagic infiltration or pigmentation. When the hemor- 
rhagic manifestations dominate the field the term "red atrophy" is 




Fig. 298. — Acute yellow atrophy of the liver, showing extensive fatty degeneration and in 
places complete destruction of the liver-cells (Kast and Rumpel). 

given. The process usually begins in the left lobe, but rapidly involves 
the entire organ. Sometimes the liver is increased in size during the ini- 
tial stages, and occasionally a liver enlarged by previous disease suffers 
terminal acute atrophy. 




Fig. 299. — Acute yellow atrophy of the liver from a case occurring during pregnancy. 

Microscopically, the hepatic cells are found to have undergone 
rapid fatty degeneration or necrosis, and are filled with or replaced 
by yellowish pigment particles. The fat seems to be both in protoplasm 
and nucleus. At times there seems to be attempts at regeneration of 



DISEASES OF THE GASTROINTESTINAL TRACT 



661 



the liver-cells. Interstitial round cell increase is noted. As the process 
advances the cells are completely destroyed (Fig. 298). In the red 
areas referred to infiltration with blood-cells and hematogenous pig- 
mentation are observed. In the liver of pregnancy degenerations 
begin in the central and midlobular regions (Fig. 299). 

Associated Conditions. — Acute yellow atrophy leads to intense 
cholemia, in consequence of which biliary pigmentation of the various 
structures of the body may develop. Petechial hemorrhages may occur 
in the mucous or serous membranes or in the skin. The urine contains 
leucin and tyrosin. More or less profound acid intoxication may occur. 
(See Acid Intoxication, Part I.) 

Amyloid infiltration occurs in consequence of syphilis, tuberculosis, 
and suppurative diseases of the bones, or as a result of long standing 
cachexia. It is habitually associated with amyloid disease of the 
spleen, and often of the kidneys and other structures. 

Amyloid infiltration begins in the smallest blood-vessels between 
and within the acini, causing a more or less pronounced thickening of 
their walls. The liver-cells themselves may be secondarily involved, 
but more frequently undergo atrophy 
and fatty degeneration in consequence 
of the pressure and of diminished 
nutrition due to compression of the 
blood-vessels (Fig. 300). 

The liver is enlarged, denser than 
normal, its edges rounded, and the 
tightly drawn capsule is smooth and 
glistening. Not rarely it presents a 
striking translucency, and on section 
the color is grayish white or yellow. 
The peripheral and central zones of 
the acini are sometimes readily dis- 
tinguished by their light color from 
the innermost portions, which are 
least affected. 

Dropsical infiltration of the liver-cells occurs in cases of intense 
infection and intoxication, especially such as originate in some part of 
the portal circulation. It is found particularly in the vicinity of necrotic 
areas due to embolic occlusion of the interlobular portal veins. The 
liver substance is swollen, and, microscopically, the cells are cloudy and 
ofttimes vacuolated. The cells and columns are pushed apart by the 
fluid. 

Necroses of the liver occur as large areas or in small foci. They 
are found in infections and intoxications, the former causing focal, 
the latter massive, lesions. The pathological alteration is coagulative. 
The focal necroses of typhoid fever, septicemia, and the like are small 
opaque, yellowish-gray, ill-outlined dots in the parenchyma, giving the 
microscopical appearance as outlined under Necrosis (q. v.). 




Fig. 300. — Amyloid liver (from a photo- 
graph by Dr. Wm. M. Gray). 



662 



A TEXT-BOOK OF PATHOLOGY 



INFLAMMATIONS 

Hepatitis, or inflammation of the liver, may be of several forms: a 
parenchymatous, an acute interstitial, or a chronic interstitial. 

Parenchymatous Hepatitis. — In the course of various infections 
and intoxications a certain amount of parenchymatous degeneration 
of the liver-cells may take place. This was formerly described under 
the name "parenchymatous hepatitis." The term is generally in- 
appropriate, though in some instances there is associated with the 
degeneration of the hepatic cells a certain amount of cellular infiltration 
and reactive inflammation. To such cases the term "parenchymatous 
inflammation" might be applied, though, in reality, even these are more 
degenerative than inflammatory in nature. To the combination the 
term "acute diffuse hepatitis" may be applied. The lesion is com- 
moner in the general infections of the lower animals than in man. 
It is sometimes impossible to say which structure, parenchyma or its 
support, is affected most. 

Acute Interstitial Hepatitis and Abscess of the Liver. — Bac- 
teria may gain access in several ways. In some cases penetrating 
wounds, or perforation of gastric or duodenal ulcers or of other pathol- 
ogical lesions into the liver, occasion direct infection. In other cases 
the micro-organisms are carried in the circulation and enter the liver 
with the portal or hepatic blood, or by retrograde embolism through the 
hepatic veins from the vena cava. Finally, infection may occur by 
invasion of the bacteria along the bile-ducts. 

Most frequently hepatic abscess is secondary to ulcerative disease 
of the intestines, notably dysentery. In this disease the specific amebae 
are carried to the liver in the portal circulation, and occasion necrotic 
foci in which the bacteria carried with the amebse multiply and give 
rise to the further changes constituting an abscess. Similar embolic 
abscesses occasionally follow appendicitis and perityphlitis, or various 
forms of intestinal ulceration. Thrombophlebitis of the portal vein 
not rarely extends to the smaller branches within the liver, and occa- 
sions multiple suppurative foci. 

In cases of general pyemia multiple abscesses of the liver may 
occur, especially when the primary infection occurs within the abdomen. 
Infection by invasion along the biliary tract is especially prone to occur 
when there is obstruction of the bile-ducts by calculi or otherwise. In 
tropical countries traumatism without visible contusion may lead to 
abscesses, and it is not unlikely that micro-organisms from the biliary 
passages penetrate the hepatic structure in the injured portions. 

Among the micro-organisms that have been discovered are the 
streptococci and staphylococci, the Bacillus coli communis, and others 
less frequently. 

Pathological Anatomy. — Dysenteric and traumatic abscesses are 
usually solitary, and generally occupy the right lobe. In the early stages 
they appear as spots of grayish or yellowish color, in which the division 
of the lobules is lost and which assume a more and more granular ap- 



DISEASES OF THE GASTROINTESTINAL TRACT 



663 



pearance. Subsequently softening takes place and a cavity is formed. 
This increases in size until, in advanced cases, it may reach enormous 
proportions. The contents consist of curdy or creamy pus having a 
yellowish, brownish, or often quite reddish appearance, and the wall is 
composed of an ill-formed pyogenic membrane. The abscess may 
consist of a single cavity or may be partially lobulated. Sometimes 
there are multiple abscesses. If the cavity is small, resorption of the 
pus may take place and a cicatrix may result. In other cases inspissation 
and encapsulation ensue. Large abscesses may rupture into the pleura, 
into the stomach or intestines, into the peritoneal cavity, or externally. 




Fig. 301. — Cirrhosis of liver due to chronic passive congestion. 



Not rarely the diaphragm and lungs are penetrated, and the pus is evacu- 
ated through the bronchi. 

Metastatic abscesses, and those due to infection from the biliary 
ducts or to suppurative pylephlebitis, are multiple and usually of small 
size. 

Chronic Interstitial Hepatitis or Cirrhosis of the Liver. — These 
terms are applied to a group of affections characterized by more or less 
diffuse hyperplasia of the connective tissue of the liver, usually most 
pronounced in the interlobular tissues and surrounding the branches 
of the portal vein, but sometimes invading the lobules themselves. 
Secondary atrophy or, less commonly, certain atypical forms of hyper- 
plasia of the liver-cells follow after the connective-tissue hyperplasia. 



664 



A TEXT-BOOK OF PATHOLOGY 



In some instances the capsule of the liver is also involved in the fibrous 
overgrowth. 

The etiology of cirrhosis is still in many respects obscure. The irri- 
tants, toxic agents or bacteria, may reach the liver through the portal 
vein, the hepatic artery, the biliary channels, and possibly via the lym- 
phatics or the peritoneal covering of the organ. The most important 
routes are the portal vein and the bile-ducts, as either of these fur- 
nishes a possible path for the entrance of the many forms of micro- 
organisms that may occupy the intestinal tract; the portal vein in par- 
ticular may convey poisons ingested or manufactured in the stomach 
or intestines. The occurrence of cirrhosis following certain general 
infections (scarlatina, malaria, syphilis) suggests the possibility that 
the causative agents may enter through the hepatic artery — that is, 
from the systemic arterial blood. 




Fig. 302. — Atrophic cirrhosis of the liver (Laennec type). 

A form of hepatic fibrosis that, pathologically speaking, may be 
regarded as chronic interstitial hepatitis is that which follows long- 
standing congestion of the liver in cases of cardiac disease, emphysema 
of the lungs, and other causes of stasis in the inferior vena cava. The 
terms cirrhosis from passive congestion and cardiac cirrhosis are some- 
times used. In this condition the central veins of the lobules are over- 
distended, and pressure-necrosis of the surrounding liver-cells followed 
by endothelial hyperplasia and intralobular fibrosis are later develop- 
ments. The cross-section of the liver shows a variegated appearance, 
due to the dark (congested) central zone of the lobules and the lighter 
colored periphery. The term nutmeg-liver indicates this stage. Finally, 
the fibrosis becomes more extensive, and the whole organ is more or 
less deeply stained with blood-pigment (red atrophy or induration). 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



665 



Localized areas of fibrosis may occur in the liver, as in any organ 
around tumors, granulomatous processes, or any pathological area. 

Varieties of Cirrhosis. — Two types of cirrhosis, sufficiently dis- 
tinctive in their pathological and clinical features to be regarded as 
separate entities, are the portal and the biliary. The older terms, 
atrophic and hypertrophic, are falling into disuse as less distinctive. A 
portal cirrhosis may be atrophic or hypertrophic, and a biliary cirrhosis 
is not of necessity hypertrophic. 

Portal Cirrhosis. — Gin-drinker's liver, Laennec's cirrhosis, is an inter- 
lobular increase of connective tissue causing compression of lobules and 
portal radicles (Fig. 302). It is the commonest form of cirrhosis of the 
liver, and has been ascribed to excessive use of spirits, especially raw. 




Fig. 303. — Fatty alcoholic cirrhosis. 



There seems to be small doubt that sedentary life, gastro-intestinal dis- 
orders, and alcohol predispose to this form; an opinion not at all incon- 
sistent with the present idea of its immediate causation. It is gener- 
ally ascribed today to toxic agents passing in through the portal vein, 
causing necrosis of the adjacent liver-cells, a round-cell infiltration 
about the radicles of the portal vein, fatty metamorphosis, connective- 
tissue overgrowth, and secondary contraction. This affects the nutri- 
tion of the liver parenchyma, favors continuance of degeneration, and 
so squeezes the softer tissue that a roughening of the surface results 
(hob-nail liver). 

It has been suggested that the colon bacillus may be a factor in 
the causation of portal cirrhosis, since it will induce fibrosis when gain- 
ing access to a liver already the seat of necrosis or fatty change, a theory 



666 



A TEXT-BOOK OF PATHOLOGY 



fairly well supported by experimental evidence. Chronic gastrointes- 
tinal disease, often a forerunner of cirrhosis, gives ample opportunity 
for focal or diffuse loss of resistance in the liver, because considerable 
amounts of toxic substances are formed and so pass through this organ 
in the portal circulation. The constant use of alcohol, a habit undoubt- 
edly favoring cirrhosis, supplies an easily oxidizable substance to the 
liver, and food fat, not so easily burned, is stored, thus acting as a great 
burden for the cell, so that bacterial infection is met with no resist- 
ance, the cell succumbs, and fibrosis follows (Fig. 303). The older 
idea that alcohol acts as a direct irritant to the hepatic cells and by 
destroying these initiates the cirrhotic process cannot as yet be thrown 
aside. 

Morbid Anatomy. — In the earliest stages the liver is often enlarged, 
but in the typical advanced form it is contracted, extremely hard, 




Fig. 304. — Atrophic cirrhosis of the liver of a boy aged sixteen years, showing also thick- 
ening of the capsule and ligaments (perihepatitis). 

granular or irregularly uneven on the surface, and, on section, resistant 
to the knife (Fig. 304). The size of the liver, even in advanced stages, 
is by no means always small. A study of statistics obtained at the post- 
mortem table shows that the liver in perhaps a majority of the cases of 
otherwise typical Laennec's cirrhosis is larger than the normal organ. 
This is due to fatty infiltration of the liver-cells, to associated congestion, 
or to an attempt at replacement of lost parenchyma by hypertrophy or 
hyperplasia. This attempt is transient and ineffectual. The highly 
fatty cirrhosis of the interlobular type gives a liver of egg-yolk color. 
The surface of section presents bands of connective tissue surrounding 
groups of acini, and compressing them so that they rise above the sur- 
face. The connective-tissue bands are dull gray or white in appear- 
ance, the enclosed acini yellowish or brownish. 



DISEASES OF THE GASTROINTESTINAL TRACT 



667 



The growth of connective tissue follows its usual course of excess, 
and is shortly found as wide, irregular bands, rather poor in cells, 
separating the lobules ("unilobular"). It may instead embrace a group 
of lobules, giving rise to the so-called "multilobular cirrhosis." 

Microscopically, cirrhosis is characterized by a proliferation of the 
connective tissues around the interlobular branches of the portal vein. 
In the earlier stage this occurs in the form of round-cell infiltration 
and proliferation of fibroblastic cells, causing moderate obstruction to 
the portal circulation. Later, the connective tissue becomes sclerotic, 
greater compression of the portal veins ensues, and considerable ob- 
struction of the circulation results. At the same time the acini are 
compressed and suffer degeneration and atrophy. The atrophic lobules, 
with their degenerated and pigmented liver-cells, may be a striking fea- 
ture in the histological picture. There is little tendency to extensive 




Fig. 305. — Cirrhosis of the liver, showing a lobule in the center surrounded by dense 
connective tissue. The hepatic cells within the lobule are extensively degenerated (fatty), 
and those at the periphery deeply pigmented. 

invasion of the acini themselves by the inflammatory process. New- 
formed biliary ducts may be present in considerable numbers in the 
hyperplastic interlobular tissue. 

Associated Changes. — The marked result of atrophic cirrhosis is 
obstruction to the portal circulation. This occasions congestion of the 
spleen and gastro-intestinal mucosa and, eventually, ascites. When 
the obstruction becomes extreme, collateral circulation may relieve 
the congestion of the portal system. The most prominent anastomoses 
are those between the gastric and esophageal veins, and between the 
hemorrhoidal veins and the veins of Retzius with the retroperitoneal 
veins. The veins of the round ligament increase in size and may com- 
municate with the superficial veins at the umbilicus (caput medusa?). 

Gastro-intestinal catarrh and enlargement of the spleen are usually 
prominent in cirrhosis. Jaundice is rare, because the bile-ducts are rarely 
compressed. There may be a low-grade cirrhosis of the pancreas. 



668 



A TEXT-BOOK OF PATHOLOGY 



In some instances the liver is large and smoother, softer and lighter 
in color, from the fact that considerable fatty infiltration of the acini is 
associated with the cirrhosis (fatty cirrhosis, Figs. 303 and 305). This 
is the so-called "beer-drinker's liver." In one case, in a small man seen 
by one of the authors, the organ weighed 9| pounds. In the later stages 
such cases may become converted into the typical form by absorption 
of the fat. 

Pathological Physiology. — Cirrhosis of the liver occasions gastro- 
intestinal symptoms by obstructing the portal circulation, and prob- 
ably also by altering the functional action of the liver. Metabolic 
disorders of some sort also result from the hepatic disease, but the nature 




Fig. 306. — Biliary cirrhosis of liver. 



of these is as yet unknown. There is often a toxic state with delirium, 
the exact cause of which is not understood. The fatal termination 
often comes in the form of sudden or gradual coma, which is probably 
toxemic. 

Biliary cirrhosis is a form accompanied by inflammatory, obstruc- 
tive, and pigmentary changes in or surrounding the bile-duct system. 
Any one of these may dominate the pathological picture (Fig. 306). 

Two types have been described: In the first, obstructive biliary cir- 
rhosis, the hepatic disease follows obstructions of the biliary ducts, 
and is, therefore, largely of mechanical origin; in the second, Hanoi's 
hypertrophic cirrhosis or true biliary cirrhosis, gross obstruction of the 



DISEASES OF THE GASTROINTESTINAL TRACT 669 

ducts does not precede the hepatic disease. At most, catarrhal chol- 
angitis precedes or accompanies the disease and may in part occasion 
the associated jaundice. 

Obstructive biliary cirrhosis is a fibrous overgrowth due to back 
pressure upon bile channels, which causes stagnation, peribiliary con- 
gestion, liberation of irritative pigment, reactive tissue change, and 
fibrosis. The obstruction may be due to gall-stones, tumors, or atresia 
of the bile-ducts. 

The appearance of the liver is much the same as that seen in hy- 
pertrophic cirrhosis of the Hanot type. The organ is uniformly en- 
larged, and may be somewhat granular upon the surface or entirely 
smooth. On section, the substance is found to be deeply bile stained, 
and has a yellowish or greenish color. The substance is firm, and the 
overgrowth of connective tissue may be visible on the surface. Bile- 
ducts, distended and irregular, are to be seen. 

Microscopically, the first discoverable changes are areas of insular 
necrosis in the peripheral zones of the acini. Subsequently, prolifera- 
tion of connective tissue replaces these and spreads to the interlobular 
tissues. Proliferation around the interlobular biliary capillaries (peri- 
angiocholitis) may be a striking characteristic from the first, and multi- 
plication of new bile-ducts and of hepatic cells is observed. In cases of 
absolute obstruction of the gall-ducts, and in cases in which active 
chemical changes in the bile have occurred, rapid fatty degeneration 
and acute atrophy of the liver may be the terminal phases. The 
spleen is little, if at all, enlarged, and ascites does not occur until very 
late, if at all. 

Hanot's cirrhosis is a diffuse increase in fibrous tissue following 
the bile-ducts and associated with inflammatory changes in and around 
them. The cause is generally thought to be an infection traveling up 
the biliary system. By reason of the association of bile-ducts in the 
interlobular septa with the intralobular bile radicles the infiltrative and 
proliferative processes invade the outer sections of the lobules and do 
not remain so largely interlobular as is the case in Laennec's cirrhosis. 

Microscopically, proliferation in the interlobular connective tissues 
is found, as in the atrophic form, but it does not bear the same relation 
to the portal veins and is less prone to cicatricial contraction. Unlike 
the portal form, there is decided extension into the peripheral zones 
of the acini, and everywhere between the columns of hepatic cells 
there may be seen proliferated fibroblastic cells. This inward extension 
of the fibrous tissue separates and distorts segments of bile radicles 
and small ducts near the lobular border, giving the appearance of 
many newly formed bile-ducts. There is, indeed, an actual increase of 
bile-ducts. Their prominence on section seems due to an attempt at 
regeneration by peripheral parenchyma cells. All these changes are 
accompanied by biliary pigmentation, manifested both in the organ 
and generally in the body. There is no obstruction to the portal or 
gastric circulation, so that ascites and varices do not occur. The spleen 
is always enlarged and sometimes decidedly so. 



670 



A TEXT-BOOK OF PATHOLOGY 



Pigmentary Cirrhosis. — Certain rare forms have been ascribed to 
carbon, but the most important is that associated with hemosiderosis, 
due probably to excessive blood destruction, and associated with the 
bronzed diabetes of chronic pancreatitis. Again, in Banti's disease, with 
its excessive hemolysis, probably due to increased splenic activity, 
there is a pigment collection in the liver which may lead, in the advanced 
stages, to a cirrhosis. 

Large scars may occur after massive destruction of liver tissue, 
in acute yellow atrophy, poisoning, gummata, etc. These have been 
called "toxic cirrhoses," but it is well to remember that they represent 
finished reparative processes, and do not tend to spread. Of this 

nature may be the fibrosis in the 
vicinity of tuberculomata, which 
some authors have called "tuber- 
culous cirrhosis." 

Perihepatitis. — Inflammation 
of the capsule of the liver and of 
the superficial portions of the he- 
patic structure may be associated 
with cirrhosis (Fig. 307), and not 
rarely occurs in consequence of 
chronic peritonitis. It may lead 
to considerable thickening of the 
capsule. The pressure of the con- 
tracting fibrous tissue may occa- 
sion atrophy of the underlying 
hepatic substance, and a more or 
less uneven and atrophic organ 
results. Primary inflammation of 
the capsule may be an expression 
of syphilitic infection, and may occur alone or in association with 
thickening of the peritoneum. Reference will be made, in the dis- 
cussion of diseases of the peritoneum, to a special form of hyperplastic 
perihepatitis — that known as the Zuckergussleber of Curschmann. 

Syphilitic cirrhosis is to be mentioned because of its common occur- 
rence in congenital syphilis. The liver is large and hard, and the 
fibrosis is pericellular, separating not only liver columns, but the cells 
themselves. Gummata are usually present. Spirochetes are exceed- 
ingly numerous. 

HYPERTROPHY 

The regeneration after injuries of the liver shows the power of the 
liver-cells to undergo active multiplication. Not rarely, active hyper- 
plasia of liver-cells, from liver-cell or bile-duct epithelium, throughout 
the entire organ may occur in association with other diseases, notably 
hypertrophic cirrhosis. A simple hypertrophy of the liver also occurs 
in certain well-developed, robust individuals. Enlargements of the 
liver formerly regarded as hypertrophies are, for the most part, due to 
pathological conditions. 




Fig. 307. — Perihepatitis associated with cir- 
rhosis of the liver. 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



671 



Regeneration of healthy liver can take place when a portion has been 
destroyed by injury. The hypertrophic and hyperplastic cells in this 
case and in cirrhosis are large, sharply outlined, and take the stain more 
deeply. Bile-duct epithelium seems to be able to generate liver-cells. 

RUPTURE OF THE LIVER 

Rupture may occur from direct traumatic injury, and is particu- 
larly common in the newborn when forcible delivery has been neces- 
sary. In the latter cases small injuries with secondary hemorrhagic 
infiltration are observed near the surface of the organ. Portions of 
liver-cells may be loosened and may be carried as emboli to the lungs. 
The injury is repaired by active hyperplasia of the liver-cells and of the 
biliary capillaries, and in this manner the affected part may be restored 
without the development of scar tissue. Large injuries, however, occa- 
sion the formation of cicatricial tissue. 

INFECTIOUS DISEASES 

Tuberculosis may occur in the form of minute, translucent, miliary 
tubercles, which may be scarcely visible to the naked eye (Fig. 308), 
or in the form of larger foci. Tuberculosis of the liver is always a sec- 
ondary disease. The tubercles arise 
in the interlobular tissue or in the 
acini themselves. The larger case- 
ous tubercles are rare ; they may be 
associated with a local or diffuse 
sclerotic contraction of the organ. 
The association of general cirrhosis 
and a tuberculous lesion is frequent, 
but probably accidental. In the im- 
mediate vicinity of a caseous mass 
connective-tissue overgrowth always 
occurs, and caseous masses may 
become encapsulated. Bile-duct 
tubercles occur along the course of 
these tubes, and may ulcerate into 
the lumen. Miliary tuberculosis of 
the capsule of the liver not rarely 
occurs in tuberculous peritonitis. 

Syphilis is met with in the form of diffuse infiltration and cirrhosis, 
or in the form of gummata. Either of these varieties may be found as 
a result of acquired or of hereditary syphilis. In the diffuse form the liver 
presents much the same appearances as in atrophic cirrhosis, but as the 
connective-tissue bands are much more pronounced, the liver is prone to 
be irregularly contracted and lobulated — hepar lobatum (Fig. 309). 
Gummata may occur in any part of the organ, and may be single or 
multiple, massive or miliary, presenting themselves as rounded, yellow- 



4 -,'J' S S&.'fS 



Fig. 308. — Miliary tubercles in the liver. 



672 



A TEXT-BOOK OF PATHOLOGY 



ish, or grayish areas, ofttimes showing central necrosis and surrounded 
by connective-tissue hyperplasia (see Fig. 119). Complete cicatrization 
may lead to decided scar formation. In addition to these forms, con- 
genital syphilis may manifest itself in the form of a uniform, diffuse con- 




Fig. 309.— Syphilitic cirrhosis of the liver: lobulated liver (Kast and Rumpel). 

nective-tissue hyperplasia and round-cell infiltration. The liver-cells 
are pushed apart and are ill-developed or atrophic (Fig. 310). 

Leprosy occasionally affects the liver, causing the formation of 
nodular masses. 




Fig. 310. — Diffuse congenital syphilis of the liver. 



Actinomycosis, primary or secondary, occurs in the liver as single 
or, more commonly, multiple abscesses with granular necrotic contents, 
surrounded by a productive deforming connective tissue, and tending 
to cause adhesions through which the process travels to adjacent struc- 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



673 



TUMORS 

Fibromata, lipomata, and myomata are occasionally observed as 
nodular masses, but have little significance. 




Fig. 311. — Section through a large nodule of sarcoma of the liver, showing the practically 
normal liver substance above, and the sarcoma with central softening below. 

Angioma is an important tumor occurring upon the surface of 
the organ; it is usually of small size, rarely exceeding that of a wal- 

43 



674 



A TEXT-BOOK OF PATHOLOGY 



nut. It is more commonly found in persons who have died at ad- 
vanced years than in young persons. Angiomata appear as dark-red 
or bluish, slightly elevated areas, either sharply outlined and encap- 
sulated, or merging gradually into the surrounding tissue. Micro- 
scopically, they are found to be cavernous angiomata or cavernomata, not 
true tumors, and doubtless owe their origin to dilatation of the capil- 
laries, with coincident atrophy of the liver-cells. Some are associated 
with hyperplasia of the vascular endothelium and belong to the hem- 
angio-endotheliomata. 

Various explanations have been given for these tumors, among the 
theories being developmental defect, capillary distention, and true 
neoplastic growth. Only those associated with endothelial change can 
properly be called neoplasms. 




Fig. 312. — Cirrhotic cancer of the liver (Hanot and Gilbert). 

Sarcoma of the liver may occasionally be primary, but is exceed- 
ingly rare (Fig. 311). Secondary sarcoma, on the other hand, is very 
common, especially the melanotic form following primary sarcoma of 
the eye. 

Lymphadenomata are frequent in the liver in the course of the 
generalization of leukemic lymphadenoma; they are best considered as 
mere infiltrations of lymphocytes consequent upon the enormous leuko- 
cytosis of this disease, but they may represent, of course, hyperplasias 
of preexisting lymph-cell collections. 

Adenoma of the liver is met with in several forms. There may be 
either nodular masses, more or less encapsulated and of grayish-white or 
pinkish color, or a form of diffuse infiltration of the liver substance by 
encapsulated nodules of similar character. Considerable cirrhosis of the 



DISEASES OF THE GASTROINTESTINAL TRACT 



675 



liver may be associated with the latter cases, and they cannot be clearly 
distinguished from cirrhotic cancer (see below). 

Carcinoma of the liver is rather rare as a primary tumor, but, like 
adenoma, may be nodular or diffuse. The nodular or massive cancer 
appears as a single mass of varying size, ofttimes surrounded by local 
metastatic nodules. On section, the color is grayish or pinkish, and there 
may be central necrosis and softening. Diffuse hepatic cancer occurs as a 
widespread and more or less uniformly distributed infiltrating growth. 
Not rarely in such cases there is associated cirrhosis, and the maero- 
scopical appearance of the liver may be strikingly like that of an ordinary 
cirrhosis, though the liver is sometimes much enlarged (Fig. 312). The 
terms cirrhotic cancer and cancer with cirrhosis have been applied to 
this form. Finally, the diffuse form may surround and spring from the 



Fig. 313. — Secondary cancer of the liver: a, Columns of liver-cells filled with bile-pig- 
ment; 6, endothelial walls of capillaries; c, carcinomatous emboli in the capillaries (Hanot 
and Gilbert). 

periportal structures, and may ramify in the form of an interlobular in- 
filtration. Microscopically, the cancers are simple or adenomatous. 

Formation and Structure of Adenomata and Carcinomata. — Micro- 
scopically, there is no sharp dividing-line between these growths. The 
adenomata present tubular formations of a more or less elongated and 
tortuous character, composed of cylindrical or of more irregular-shaped 
epithelial cells. In some instances these are strikingly like new-formed 
biliary capillaries, and perhaps they occasionally originate from these 
structures. More commonly, however, the origin would seem to be 
from the hepatic cells themselves. The columns of hepatic cells undergo 
proliferative change, and at the same time become somewhat trans- 
formed, assuming the tubular arrangement of adenoma. Occasionally 
adenoma and cystic adenoma originate from the mucous glands of the 




c 




676 



A TEXT-BOOK OF PATHOLOGY 



larger biliary ducts. When cirrhosis is associated with adenomatous 




Fig. 314. — Metastatic nodules of carcinoma on the surface of the liver (Hanot and Gilbert). 

proliferation it is probable that the primary change is a cirrhotic over- 
growth which induces secondary hyperplasia of the epithelial cells, in- 
stead of degenerative changes, such as 
usually result from the pressure of new- 
formed fibrous tissue. 

Carcinoma of the liver is similar in 
origin and structure to adenoma. The 
cellular acini and tubules are more ir- 
regular, and there is an evident tend- 
ency to diffuse infiltration and atypical 
formation of acini. 

Secondary carcinoma of the liver 
is very common as a result of carcinoma 
of the stomach or of other parts of the 
portal distribution. It is usually due 
to cancerous embolism in the portal 
capillaries, with subsequent develop- 
ment of the emboli (Fig. 313). The 
liver becomes enlarged, and presents 
nodular masses upon its surface or 
within its substance. These nodules 
vary from the size of a pea to that of 
an apple, and are frequently sharply 
delimited by capsule formation, es- 
pecially those which have reached con- 
siderable size (Fig. 315). Not rarely 
the nodules are indented upon the sur- 
face (umbilicated) from central soften- 
ing or from contraction of fibrous tissue within (Fig. 314). Secondary 
cancer of the liver may also result from direct extension of cancer of the 




Fig. 315. — Metastasis of pyloric car- 
cinoma in liver. 



DISEASES OF THE GASTROINTESTINAL TRACT 



677 



stomach or of the gall-bladder and biliary ducts. In all cases the new 
growths tend to compress the bile-ducts and lead to biliary pigmenta- 
tion of the liver substance, as well as to general icterus. 

Cysts of the liver are rare. They may spring from the biliary ducts 
which have suffered simple dilatation, or from the mucous glands of the 
larger bile-ducts (cystic adenoma). Occasionally small cysts are seen 
which suggest origin from dilatation of the lymphatic channels. 

PARASITES 

Of the protozoa, coccidial psorospermice (Fig. 316) have been occa- 
sionally demonstrated in the human liver in small nodular tumors ; but a 
more important parasite is the Entamoeba histolytica, occurring in abscess 
of the liver secondary to amebic dysentery. The pus of the abscess may 




Fig. 316. — Coccidia in the wall of a bile-duct. The cut shows in the center active pro- 
liferation of the wall of the duct, with numerous ovoid coccidia massed in the tissue. 

contain immense numbers of the amebae, and doubtless these organisms 
bear an important relation to the lesion, perhaps causing necrosis by 
their own activity and then liberating pyogenic organisms which they 
have carried from the intestines, and which complete the pathological 
process. The larval Linguatula rhinaria is occasionally met with. 

The Fasciola hepatica and the Dicroccelium lanceatum occasionally 
infest the biliary ducts, and the Schistosoma haematobium the portal vein. 
Ascarides sometimes creep upward in the biliary ducts as far as the 
branches within the liver. The Cysticercus cellulosoe is a rare parasitic 
formation. 

Echinococcus Cyst. — The most important parasitic disease of the 
liver is the echinococcus cyst, caused by the presence of the larvae of the 
Taenia echinococcus (see Part I). This parasite occasions cystic forma- 
tions of various kinds within the liver. The cyst has a double wall : the 
outer, of connective tissue; the inner, a parenchymatous membrane, 



678 



A TEXT-BOOK OF PATHOLOGY 



from which buds (brood-capsules) and secondary cysts are prone to 
originate. There may be a single cyst containing clear liquid of low 
specific cavity, or a mother-cyst containing daughter-cysts, either upon 

the inner wall or floating free within 
the liquid after their separation. 
Sometimes even granddaughter- 
cysts are formed. Occasionally the 
daughter-cysts are found outside of 
the mother-cyst, extrusion in such 
cases having taken place. A form 
of multilocular cyst is more rarely 
observed in which there are numer- 
ous small cvsts embedded in more 

lug. 31/. — Echinococcus multiloculans in' • • /t-v 

(Luschka). or less farm connective tissue (-big. 

317). Echinococcus cysts may rupture 
into the abdomen or into surrounding viscera. The most serious condi- 
tion is rupture into the vena cava, as the result of which hydatid dis- 
ease of the heart, the brain, or other organs may ensue. Bacterial inva- 
sion occasionally takes place, and abscess may result. Finally, the 
liquid contents may be absorbed, and the cyst may be reduced to a small 




Fig. 318. — Echinococcus cyst of the liver (from a specimen in the Museum of the Phila- 
delphia Hospital). 

cavity having a shrivelled wall and containing granular or caseous 
detritus (Fig. 318). Echinococcus cysts may press upon the gall-duct, 
producing jaundice, or upon the portal veins, causing ascites. 

The Biliary Ducts and Gall-bladder 
inflammations 

Cholangitis, or inflammation of the biliary ducts, is most fre- 
quently secondary to duodenal catarrh, though it may be the result of 
direct irritation by gall-stones, by foreign bodies which have entered from 
the intestine, or by parasites or bacteria. In the cases secondary to duo- 




DISEASES OF THE GASTROINTESTINAL TRACT 



679 



denitis the inflammation usually extends but a short distance upward 
from the mouth of the common bile-duct, but there may sometimes be 
more extensive involvement of the ducts, and the mucous membrane of the 
gall-bladder may be affected at the same time. The mucosa is swollen, 
more or less edematous, and secretes abundant mucus. The result is 
obstruction of the duct with retention of bile, and consequent jaundice. 

Suppurative cholangitis may occur as an independent condition in 
consequence of certain infectious diseases, but is more commonly 
secondary to obstruction of the common duct or hepatic duct. Bacterial 
invasion from the intestine or through the blood causes decomposition 
of the retained bile and inflammation of the ducts. Sometimes sup- 
purative cholangitis results from the rupture of an abscess of the liver 
into the bile-ducts. The association of cholangitis, simple or sup- 




Fig. 319. — Purulent cholangitis, showing suppuration following the biliary tract from 
the hilus, and producing abscesses, one in section (from a specimen in the collection of 
Dr. Allen J. Smith). 

purative, with typhoid fever is of considerable clinical interest. Among 
the micro-organisms discovered in suppurative cholangitis the pyogenic 
micrococci and the Bacillus coli communis are most frequent. The bile- 
ducts are filled with more or less decomposed bile or with puriform 
liquid, and the walls of the ducts, especially the larger ones, may present 
an ulcerated or necrotic appearance. Retention of bile and jaundice 
result early. Small dilatations may occur in places where the duct has 
become deeply ulcerated, and later hepatic abscesses of considerable size 
may form (Fig. 319). 

Chronic cholangitis may be the outcome of an intense acute attack 
or repeated acute attacks, but is more commonly met with as a conse- 
quence of chronic obstruction of the ducts and retention of bile. A local- 
ized form, causing cicatricial stenosis, results from intense inflammatory 



680 



A TEXT-BOOK OF PATHOLOGY 



lesions following the passage of stones. The gall-ducts in chronic cholan- 
gitis are more or less thickened, and in the cases due to obstruction may 
be considerably dilated. 

Results of Cholangitis. — In the acute form extension may take 
place to the ducts within the liver, and in case of bacterial invasion 
pericholangitis and abscesses may form. More commonly acute cholan- 
gitis leads to but a temporary overfilling of the biliary capillaries with 
bile, and, in consequence, to obstructive jaundice. When the obstruction 
is continued for a considerable length of time, reactive changes occur in 
the liver, constituting the form of cirrhosis called "biliary cirrhosis" (see 
p. 669). 

Cholecystitis, or inflammation of the gall=bladder, may result 
from extension of cholangitis, or may be due to the irritation of re- 
tained bile or of gall-stones. If it should be primary, the communicat- 
ing bile-ducts are soon involved. It is a fairly common sequel of typhoid 
fever, and the typhoid bacillus has been found in the contents of the 
gall-bladder, sometimes a considerable time after the original infection 
had subsided. In this subacute or chronic typhoid cholecystitis and 
in similar conditions there is a mild hypertrophic catarrh. This permits 
the bacteria to hide in the depths of the membrane more securely. The 
epithelium is often loosened or set free, and with the abundant mucus 
forms a nucleus for gall-stones. The acute inflammation is prone to 
assume a purulent character, and the gall-bladder may become filled with 
pus {empyema of the gall-bladder) . This may rupture, discharging into 
the abdominal cavity, into adjacent viscera, or externally. The wall of 
the gall-bladder is usually much thickened and the mucous membrane 
is swollen and ulcerated. The dependent position of the sac favors 
retention of exudate and involvement of the serous coat, which may 
eventually lead to adhesions with adjacent organs if the infection be 
not of a kind to cause rapid suppuration. If, however, the condition 
be actively suppurative, fistulous tracts may be established with other 
viscera. If bile escape into the peritoneum, inflammation and necrosis 
arise. The results of long-continued non-suppurative cholecystitis are 
either distention by complete blocking of the outlet and retention of 
the contents when the mucosa continues to produce an exudate, or an 
atrophic fibrosing change in the wall, whereby the organ shrivels. 

STENOSIS AND DILATATION 

Stenosis of the bile-ducts is most commonly the result of acute 
inflammation, causing thickening of the mucosa and accumulation of 
mucus. It may result from chronic cholangitis with cicatricial over- 
growth of connective tissue; from the impaction of gall-stones, or the 
presence of various foreign bodies, such as particles of food, mucus, 
round-worms or other parasites within the duct; from pressure by 
aneurysms, by tumors of the head of the pancreas, pylorus, duodenum, 
lymphatic glands, or of the liver; and from tumors of the gall-ducts 
themselves. Sometimes it is due to the constriction of adhesions result- 



DISEASES OF THE GASTROINTESTINAL TRACT 



681 



ing from peritonitis. Obstruction of the ducts leads to the retention 
of bile and dilatation of the ducts above, with consequent enlargement 
of the liver and jaundice. Obstruction of the cystic duct, which is most 
frequently due to the impaction of a stone, may occasion dilatation 
of the gall-bladder with dropsical liquid, in consequence of the passive 
hyperemia produced by compression of the veins at the neck of the 
gall-bladder. This condition is spoken of as dropsy of the gall-bladder. 
Sometimes suppurative inflammation occurs, and empyema of the 
gall-bladder results. 

Congenital atresia of the gall-passages is a rare condition ascribed 
to antenatal interlobular cirrhosis, due to toxins entering through the 




Fig. 320. — Suppurative pylephlebitis, showing infiltration around the bile-duets and, 
in places, as at (a), a breaking down of the duct and the surrounding tissue to form necrotic 
abscess cavities. 

placenta. It gives the changes mentioned above and causes death in 
the first year. 

Contraction of the galUbiadder, or even complete shrinkage or 
atrophy, may result from obstruction at the mouth of the cystic duct, 
or from inflammatory processes within its walls or surrounding it. 

Dilatation of the ducts or of the gall-bladder most frequently 
results from any stenosis of the ducts below. 

GALL-STONES; CHOLELITHIASIS 

Gall-stones are concretions resulting from inspissation of bile, or 
from the deposit of various substances from the bile. Most frequently 
they are formed in the gall-bladder; occasionally they originate in the 
bile-ducts. 

Etiology. — The causes are imperfectly understood. Advanced 
years, the female sex, sedentary life, and high living seem to be factors of 
importance. Inflammatory conditions leading to obstruction and 
retardation of the outflow of bile, and also to desquamation of epi- 
thelium, which, with mucus, serves to form the nuclei of the stones, 



682 



A TEXT-BOOK OF PATHOLOGY 



seem to be among the causes. Besides these conditions there are prob- 
ably indefinite alterations of the bile which permit of precipitation 
of some of its constituents, notably cholesterol. Bacteria play an im- 
portant role in many cases. The bacteria may by their precipitation and 
clumping form the nucleus of a stone, or may occasion decomposition of 
the bile and inflammation of the ducts. Desquamated epithelial cells 
and products of decomposition of the bile in the latter case form the 
nucleus of the gall-stone. Among other micro-organisms the typhoid 
and colon bacilli are of etiological importance. They are able to live for 
long periods in the gall-bladder. 




Fig. 321. — Gall-bladder from a case of chronic cholecystitis with cholelithiasis. The 
interior of the gall-bladder is shown with its ribbed projections and intervening pouches, 
in which small and large gall-stones had been lodged. 

t 

Structure and Pathological Anatomy. — Gall-stones may be single 
or multiple, and may vary in size from minute granular particles of 
biliary sand to calculi several centimeters in diameter. When single 
they occur as rounded or oval masses; when multiple they are prone to 
be marked with facets; when formed within the bile-ducts they are 
elongated. Biliary sand is, for the most part, composed of biliary pig- 
ments, bilirubin in combination with calcium salts. The larger stones 
on section usually show a central nucleus composed of epithelium or 
mucus mingled with inspissated bile, surrounded by a zone of somewhat 
radiating and crystalline structure, composed of cholesterol. Around 
this may be a coat of bile-pigment. In other cases the entire stone is 



DISEASES OF THE GASTROINTESTINAL TRACT 



683 



formed of biliary pigments in combination with calcium salts or, more 
rarely, the calculus consists entirely of carbonate of lime. 

It seems that when stones form in a bladder that has been isolated 
from the liver by fibrous tissue or compression, they are usually choles- 
terol derived from the bladder wall. On the other hand, when there is 
continued inflammation, but with no hindrance to the ingress of bile 
from the liver, stones are mostly of bile-pigments, precipitated by bac- 
teria probably, and calcium salts from the inflammatory exudate. 

Gall-stones may lie in the gall-bladder or ducts without causing 
serious disturbances, or from time to time attacks of biliary colic denote 
their passage through the ducts to the bowel. They may pass through 
the ducts into the intestine when of small size, but often become im- 
pacted in the lower part of the common duct, generally just above 
the duodenal papillae or in the mouth of the cystic duct. Secondary 
changes in the gall-bladder (dilatation and inflammation) and in the 
liver (enlargement, cirrhosis) may result; and the stone may cause local 
ulceration, and may finally escape into the bowel or into other parts by 
ulceration. Occasionally gall-stones remain impacted for long periods 
without causing serious disturbances, enough space remaining to per- 
mit the escape of bile. 

TUMORS 

Tumors of the biliary tract are more common than formerly thought, 
and are almost always malignant epithelial growths. Primary carci- 
noma arising from the mucous glands, either at the fundus or neck, which 
places are those at which a stone would exercise most pressure, is the most 
important. It is usually columnar-celled carcinoma of the adenoma type. 
It appears as an irregular elevation of the mucous surface, and rapidly 
infiltrates the adjoining parts. In cases of primary cancer of the gall- 
bladder the liver is soon involved. Gall-stones are present in a great 
majority of the cases and probably play an important etiological part 
by their continuous irritation. On the other hand, the gall-stones may 
form in consequence of the stagnation of bile and other local conditions 
caused by the tumor. Secondary carcinoma of the gall-bladder or ducts 
most frequently results from cancer of the liver. The lower end of the 
duct may be involved in cases of carcinoma of the papilla of Vater. 
Sarcoma, fibroma, and other tumors are rare. 

JAUNDICE 

Jaundice, or icterus, is a discoloration of the skin and other parts, 
resulting from the presence in the blood of biliary pigments. 

Etiology. — Jaundice has been described as being of two forms: the 
obstructive mechanical or hepatogenous, and the non-obstructive or hematog- 
enous variety. This distinction has been questioned on the assump- 
tion that bilirubin can only be formed in the liver. Late observations 
would seem to indicate that under certain circumstances such a process 
may occur in the blood, thus strengthening the above classification. 

Among the distinctly mechanical causes of jaundice the most fre- 



684 



A TEXT-BOOK OF PATHOLOGY 



quent is occlusion of the ducts by catarrhal duodenitis and cholangitis. 
To this form the term catarrhal jaundice is generally applied. Less 
commonly obstruction may be occasioned by foreign bodies, gall-stones, 
or parasites within the ducts; by the pressure of tumors of the duodenum, 
pancreas, and the lymphatic glands of the liver or of the gall-ducts 
themselves; by the pressure of aneurysms upon the ducts; or by occlu- 
sion of the biliary passages within the liver by abscess, hydatid cysts, 
hypertrophic cirrhosis, carcinoma or other tumors. Congestion of the 
liver may lead to jaundice by the swelling of the organ consequent upon 
the overfilling of the vessels with blood, or by reason of the resorption of 
bile due to the alterations of pressure of the blood in the different vascu- 
lar channels. Hematogenous jaundice was formerly regarded as due to 
disintegration of the blood in the general circulation, but it is now recog- 
nized that formation of the pigments normally takes place in the liver, 
the cells of that organ breaking up hemoglobin, keeping the iron, and 
using the rest of the pigment as bilirubin. From late experiments of 
Whipple and Hooper it seems that under certain circumstances bilirubin 
may be formed without the function of the liver, and a true hematogenous 
jaundice arise. There are instances of jaundice in which active hemolysis 
in the circulation is an element of importance, probably when the liver 
cannot care for all the liberated pigment as indicated above. Jaundice 
of this character occurs in various severe infections, such as yellow fever, 
acute yellow atrophy of the liver, the jaundice of the newborn, and in 
consequence of certain intoxications (phosphorus, toadstools, the venom 
of snakes). Several explanations may be applied to cases of this kind. 
Sometimes excessive blood destruction leads to formation of abnormally 
large quantities of bile (polycholia) , and, in consequence, to absorption of 
biliary pigment by the lymphatics in the liver. It is believed by some 
investigators that the hepatic cells may in some conditions reverse the 
direction of their secretion, so that the bile is discharged into the lymph- 
atic current instead of into the biliary capillaries. This view needs con- 
firmation. In other cases toxic degeneration of the hepatic cells may lead 
to stimulation of the hepatic function, or to swelling of the cells and 
compression of the biliary capillaries, and, in consequence, to absorption 
of the bile. Finally, in the jaundice of the newborn, as well as in some 
instances of sudden emotional jaundice, disturbance of the circulation 
within the liver may be a potent cause. 

Pathological Anatomy. — Microscopical examination of the liver may 
show the biliary capillaries distended with bile and the hepatic cells 
themselves more or less pigmented. The bile is absorbed by the lymph- 
atics, and ultimately reaches the general circulation and pigments the 
tissues. The earliest evidence is seen in the intima of the vessels ; later, 
all the tissues and organs of the body may be involved, and visible dis- 
coloration appears in the skin and external mucous membranes. The 
urine is dark brownish or greenish in color, and all of the secretions 
and liquid exudates may be pigmented. In cases caused by obstruction 
of the bile-ducts the bile cannot reach the intestines and the stools have 
a quite characteristic putty color. In "hematogenous" jaundice the 



DISEASES OF THE GASTROINTESTINAL TRACT 



685 



color of the stools is to a certain extent maintained. Intense disturbances, 
especially of the nervous system, result from excessive cholemia, but 
are due to the cholic acid salts rather than to the biliary pigments. 

The Pancreas 
congenital abnormalities 

Complete absence has been met with in monstrosities. More fre- 
quently an adventitious pancreas or heterotopic pancreatic tissue is 
observed. Small nodules of pancreatic tissue may be found in the 
omentum, the wall of the intestines, or elsewhere. In a small percentage 
of cases the duct of Santorini is present as a tube of appreciable size dis- 
charging into the duodenum. 

CIRCULATORY DISTURBANCES 

Active hyperemia occurs during digestion and in association with 
acute inflammation. 

Passive hyperemia occurs in cases of obstruction to the portal 
circulation, but rarely leads to notable changes. The grayish-blue color 
is characteristic. 

Hemorrhage may occur in the pancreas, in the form of minute 
petechia? or diffuse hemorrhagic infiltration, as the result of passive 
congestion or of various hemorrhagic and infectious diseases, such as 
purpura, scurvy, septicemia, or the extreme anemias. 

Large hemorrhages occur in what is called "acute hemorrhagic pan- 
creatitis." By some the inflammatory nature of this condition is denied, 
but because of the cellular and serous infiltration accompanying it we 
prefer to describe it under pancreatitis and to call the hemorrhage with- 
out any infiltration "pancreatic apoplexy." Moreover, it is probable 
that some infection, recent or remote, has induced it (see below). Trau- 
matic hemorrhage does occur. 

Pancreatic apoplexy is a suddenly appearing destructive hemorrhagic 
extravasation into the organ without preceding inflammatory change, 
said to be due most often to alcohol, at times following injury, and 
occasionally occurring without discoverable cause. 

Sudden death may occur in these conditions from shock or compres- 
sion of the solar plexus, or the case may terminate in other pancreatic 
affections. Doubtless chronic indurative pancreatitis originates in this 
way in some cases. More commonly, progressive necrosis and suppura- 
tive inflammation terminate the disease. 

ATROPHY AND DEGENERATIONS 

Atrophy of the pancreas occurs in old age and as the result of maras- 
mic conditions. The entire organ is involved in such cases. Localized 
atrophy may be associated with various degenerations or other diseases 
of the organ. Thus, in carcinoma or in cirrhosis, pressure-atrophies are 
extremely frequent. 

Parenchymatous degeneration may occur in consequence of acute 
infections, and resembles the cloudy swelling of the liver, kidneys, and 



686 



A TEXT-BOOK OF PATHOLOGY 



heart occurring in the same diseases. The organ becomes somewhat 
enlarged, is softer than normal, and may at the same time be con- 
gested. Microscopically, the cells are found to have undergone granular 
change (parenchymatous degeneration). 

Amyloid infiltration is a rare condition occurring in association 
with amyloid disease of other organs. 

Pigmentation may be met with in the atrophic organ of old persons, 
or in consequence of hemorrhagic infiltration and subsequent disorgani- 
zation of the extravasated blood. Of particular interest are the cases of 
hematochromatosis affecting the pancreas, together with the intestines, 
liver, and other abdominal organs in drunkards. The affected organs in 
this condition present more or less extensive hematogenous pigmentation. 

Necrosis of small areas of the pancreas may occur in consequence 
of hemorrhagic or of inflammatory conditions. Sometimes the entire 
organ is disorganized by a form of gangrenous necrosis, especially in cases 
of pancreatitis resulting from perforation of a gastric ulcer or from ex- 
tension of other severe inflammatory lesions. This is a form of self- 
digestion due to active enzymes, liberated either by disturbance of the 
blood-supply or infection. Autolysis may occur at times as a post- 
mortem change. 

Disease of the Islands of Langerhans. — The pancreas normally 
contains small collections of round cells differing very strikingly from 
the true pancreatic cells. They are more abundant near the tail than 
the head of the organ. They are not in relation with the excretory ducts 
of the organ, but rather with the blood-vessels, and are supposed to 
make an internal secretion. Atrophy and hyaline degeneration of these 
islands have been described in association with chronic interstitial 
pancreatitis and as independent conditions. The relation of such 
lesions to diabetes is discussed below. 

Fat necrosis is a form of degeneration or necrosis peculiar to the 
fatty tissue of the pancreas and of the omentum. Most frequently 
it is found in association with acute or chronic pancreatitis, with tumors 
of the pancreas, or obstruction of its duct; but it may occur inde- 
pendently, and it may appear in the fatty tissue of the omentum with- 
out involving the pancreas. Minute foci, having a gray or white, 
opaque appearance, or, more rarely, larger areas due to confluence of small 
foci of necrosis, are found in the adipose tissues. Hemorrhagic infiltra- 
tion may be associated, and sometimes extensive hemorrhage may 
ensue. Inflammation of the pancreatic tissues around the foci of 
necrosis is common, and in some instances extensive disorganization 
(necrosis) of the pancreas occurs. 

Microscopically, the changes consist of, first, disintegration of the 
fat-drops of the adipose cells with formation of small droplets, then 
the appearance of fat-crystals within the adipose cells, and subsequently 
the disorganization of these and the formation of calcium salts of the 
fat-acids, the microscopical appearance at this stage being that of in- 
definite granular or translucent masses. The nature of fat-necrosis has 
been previously discussed (see p. 111). 



PLATE 12 




Acute hemorrhagic pancreatitis showing fat necrosis. 



DISEASES OF THE GASTROINTESTINAL TRACT 



687 



INFLAMMATIONS 

Pancreatitis may be acute or chronic. The acute variety presents 
itself in different forms, the most frequent being the hemorrhagic and 
the suppurative or necrotic. Chronic pancreatitis is analogous to 
chronic hepatitis, and leads to similar induration or cirrhosis. 

The sources of infection of the pancreas must be the blood, lymph, 
and pancreatic duct, of which the last seems the most important. In 
disturbances of the duodenum bacteria may pass from the ampulla of 
Vater along Wirsung's duct to the gland, and it has been shown 
that bile may also follow this course. Either of these factors can pro- 
duce inflammation of the duct, its sheath or adjacent acini, and lead 
to alterations in blood-supply to the whole organ or isolated lobules. 
These facts are important to remember in studying the diseases of the 
pancreas. In all forms of pancreatitis the existence of biliary calculi 
should be sought, as stones and sand, especially in Vater's ampulla, 
seem to predispose to affections of the organ. 

Acute hemorrhagic pancreatitis occurs most commonly in young 
persons, and is probably in most, if not all, cases dependent upon in- 
fection of the pancreas through its ducts, in the presence of conditions 
favoring pancreatic hemorrhage (q. v.). It is likely that some cases 
are not actively inflammatory, but simply instances of degenerations 
of the pancreas, with hemorrhage and round-cell infiltration as conse- 
quences. The pancreas is swollen, especially at its head; the lobules 
are enlarged and the interlobular tissues compressed. Hemorrhagic 
infiltration is a constant condition, but variable in extent. Micro- 
scopically, the cells of the pancreas are swollen, and usually present 
the appearances of parenchymatous degeneration. The interlobular 
tissues are infiltrated with round cells. Localized necrosis and fat- 
necrosis may be associated. Gangrenous pancreatitis is frequently 
described, but this form is probably not a special variety, being more 
likely a severe grade of the hemorrhagic disease; it is not peculiar in 
causation. Rapid death is the usual consequence, but it is probable 
that some of the cases terminate in chronic pancreatitis. There is edema 
or hemorrhage into the capsule, which may escape to the peritoneum by 
osmosis or rupture, carrying pancreatic enzymes with it. 

It is believed that the pancreatic secretion itself plays the chief role 
in the causation of this condition, since a ligation of Wirsung's duct will 
bring about an analogous inflammation. If local areas have been the 
seat of inflammation or edema, cellular necrosis will liberate the pan- 
creatic enzymes, of which steapsin will at once attack the neighboring 
fat, causing fat-necrosis, while trypsin will erode blood-vessels, per- 
mitting edema or hemorrhage. 

Acute suppurative pancreatitis may result from direct extension of 
septic processes in the neighborhood, as in gastric or duodenal ulceration, 
purulent collections in the peritoneum, and the like. It may also occur 
as an independent affection, most frequently in consequence of infection 
from the intestinal tract through the ducts, or as the effect of pyogenic 



688 



A TEXT-BOOK OF PATHOLOGY 



cocci operating in an organ devitalized by acute hemorrhagic pancreatitis. 
Occasionally metastatic abscesses are observed in the pancreas. Hemor- 
rhagic pancreatitis may be converted into the necrotic form in conse- 
quence of extensive extravasation of blood and secondary infection. 

The organ presents a variable appearance, according to the cause 
and extent of the process. There is generally marked swelling with 
more or less softening, and not rarely necrotic foci. Complete gangrene 
or necrosis is an occasional termination. In other cases parts of the 
pancreas may slough, the cast off part being retained as a sequestrum 
or discharged through the intestines or into the peritoneum, setting up 
fatal peritonitis. The great edematous swelling of the capsule in both 
the foregoing forms is worthy of emphasis. 

Chronic indurative pancreatitis, or cirrhosis of the pancreas, may 
be hematogenous in origin, resulting from syphilis and alcoholism, or 
it may be caused by prolonged irritation exercised through the pan- 
creatic ducts, calculi, either biliary or pancreatic, in consequence of 
frequent entrance of intestinal contents or partial stenosis of the ducts. 
In the latter case it may be secondary to duodenal catarrhs or obstruc- 
tions of the pancreatic duct. In some cases it is doubtless the outcome 
of acute attacks. 

The pancreas in the earlier stages is enlarged and hard, especially 
at the head, where the firmness may be that of scirrhus cancer. On 
section it may present a homogeneous structure and may be of car- 
tilaginous consistence. Macroscopically, the tissues between the acini 
are visibly infiltrated and hyperplastic, the amount of connective tis- 
sue being greatly in excess of the normal. In the later stages the organ 
becomes contracted, and may be considerably reduced in size and of 
stony hardness. 

Microscopically, the parenchyma of the organ is found to be atrophied 
or degenerated in consequence of contraction of the hyperplastic fibrous 
tissue. Fat-necrosis and fatty degeneration of the pancreatic cells are 
frequently associated. 

Interlobular and interacinar fibrosis have been described. The 
former, said to follow infection through the duct or obstruction by cal- 
culi, produces a hard nodular organ traversed by wide trabeculae which 
compress the acini and islands of Langerhans. Interacinar fibrosis, 
believed to be due to alcohol and arteriosclerosis, occurs as a connec- 
tive-tissue overgrowth within acini and islets; the organ is smooth and 
of natural size. This form is seen frequently with hepatic cirrhosis and 
diabetes. 

Pathological Physiology of Pancreatic Disease. — Among the 
more or less characteristic symptoms of pancreatic disease are fatty 
diarrhea (steatorrhea), imperfect digestion of proteins (azotorrhea), 
rapid emaciation, lipemia, and lipuria. All of these result from the 
cessation of pancreatic secretion and consequent disturbances of diges- 
tion and absorption of food. None of them is pathognomonic. A 
more important symptom is glycosuria, and the role of pancreatic 
disease in the pathology of diabetes is a leading one. Atrophy and car- 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



689 



cinoma of the organ may be found in diabetes, but the commonest 
changes are hyaline necroses of the islets of Langerhans and more or 
less regularly distributed fibrosis. Whatever the nature of the disease, 
the result seems to be a disturbance of an internal secretion having im- 
portance in the consumption of sugar. When this secretion stops or 
diminishes, glycosuria or diabetes results. While many, indeed, prob- 
ably most, cases of diabetes show pancreatic lesions either in acini or 
islets of Langerhans, there is no anatomical proof that disease of this 
organ is the cause of diabetes, although chemical studies connect the 
two physiologically. There seems to be an internal secretion of the 
organ, probably emanating from the islets, which has a part in carbo- 
hydrate metabolism. 

INFECTIOUS DISEASES 

Syphilis may occur in the pancreas in the form of indurative pan- 
creatitis or of gummata. The former may occur in adults, but is more 
common in the newborn, in association with indurative changes in the 
liver, lungs, and other organs. 

Tuberculosis of the pancreas, in the form of miliary tubercles, may 
occur in cases of generalized tuberculosis, but this organ is one of the 
rarest seats of tuberculosis in the body. 

TUMORS 

Carcinoma. — Primary cancer may affect the head or, more rarely, 
other parts of the pancreas, and is of the glandular (scirrhus) or, more 
rarely, of the cylindrical-celled variety. Compression with secondary 
cystic distention of the pancreatic duct and obstruction of the common 
bile-duct or of the veins (portal, superior mesenteric, and splenic) 
behind the head of the organ may result. Metastasis to the neighboring 
lymphatic glands and to the liver is frequent. Secondary cancer may 
affect the pancreas by extension of cancer of the stomach or of the 
duodenum. 

Pathological Physiology. — Pancreatic carcinoma and other chronic 
diseases of the pancreas often occasion rapid emaciation, and sometimes 
fatty diarrhea, lipemia, and lipuria. In a mechanical way cancer of 
the head of the pancreas may cause jaundice by obstruction of the bile- 
ducts; splenic enlargement, intestinal congestion, diarrhea, and ascites 
by obstruction of the adjacent veins ; repeated vomiting and sometimes 
intestinal obstruction by compression of the duodenum. 

Sarcoma is rarely primary. Secondary nodules are occasionally 
observed. 

Cysts of the pancreas may be of several kinds. Dilatation from 
obstruction of the pancreatic duct or its branches may occasion a 
single cyst or multiple cysts filled with serous or gelatinous liquid. 
Hemorrhagic cysts are sometimes the result of necrosis of portions of the 
organ, or a hemorrhage (hematoma) may be later converted into a serous 
cyst. The latter is the mode of formation of some of the large cysts, 
occurring, for the most part, near the tail of the pancreas. In other 

44 



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A TEXT-BOOK OF PATHOLOGY 



cases, it has been held, these cysts result from primary necrosis and 
subsequent digestion of the necrotic area by the pancreatic secretions. 
In rare instances cysts of the pancreas have a glandular structure of the 
papillary cystadenoma type. 

Cystic accumulations in the lesser omental cavity, resulting from 
localized peritonitis, may be difficult to distinguish from true pan- 
creatic cysts, as some of the latter lie more outside than within the 
pancreas. In some instances such localized peritonitis seems to be the 
result of extension of pancreatic inflammations or rupture of sub- 
capsular collections. These have been called pseudopancreatic cysts. 

The fluid of pancreatic cysts often contains a proteolytic and an 
emulsifying ferment, but the contents of other abdominal cysts may 
have similar constituents. 

The Pancreatic Duct 

Obstruction of the pancreatic duct may be due to tumors of the 
papilla in the duodenum or of the head of the pancreas, to calculi, to 




Fig. 322. — Dilatation of the pancreatic duct and atrophy of the pancreas, due to calculi 

(Orth). 

inflammatory thickening of the duct itself, or to the pressure of con- 
tracting fibrous tissue in chronic pancreatitis. Most commonly it leads 
to dilatation of the duct, this sometimes becoming so great as to occasion 
actual cystic formations (Fig. 322). The dilated ducts are filled with 
clear liquid, but sometimes through bacterial infection this is rendered 
turbid, or is actually converted into pus. Occasionally, small cysts, 
caused by distention of the finer divisions of the duct, are scattered 
through the organ {-pancreatic acne). These are supposed to result 
from catarrhal processes in the ducts themselves. These small cysts 
are filled with clear or puriform liquid. Some cases so described are 
doubtless instances of fat-necrosis. In congenital atresia of the bile- 
ducts there is frequently a similar condition in the duct of Wirsung. 
The duct of Santorini has been found stenotic also. 

Pancreatic calculi are composed of carbonate or phosphate of lime, 
and usually have an irregular shape. They may occasion cystic disten- 
tion of the ducts and abscess formation. 



DISEASES OF THE GASTROINTESTINAL TRACT 



691 



The Peritoneum 
congenital abnormalities 

Absence of the peritoneum has been described ; but more frequently 
minor defects, such as absence of the omentum or unnatural length 
of the omentum or mesentery, localized defects, fenestrations, and the 
like, have been observed. The peritoneal extension into the inguinal 
canal normally becomes occluded, but may remain patulous and may 
lead to congenital hernia. 

The defects of the peritoneum are not of great importance to this 
structure itself, but as it acts as a protective covering and support to the 
abdominal viscera, alterations in position, form, and function of the 
contents of the cavity result from congenital defects, e. g., enteroptosis 
from long mesentery. 

CIRCULATORY DISTURBANCES 

Active hyperemia may occur in association with inflammation, 
or in the vicinity of lesions within the intestine which have not yet 
occasioned actual inflammation of the peritoneum itself. The affected 
part is bright red, the arterioles being distended and the endothelium 
somewhat swollen and elevated. 

Passive hyperemia is more frequent. It may be part of a general 
venous congestion, or may result from obstruction of the portal vein by 
thrombosis, cirrhosis of the liver, and similar conditions. The venules 
may be widely dilated, the deeper layers of the peritoneum somewhat 
edematous, and the lining endothelium swollen and loosened. Intense 
passive congestion may lead to ascites or to hemorrhage. 

Hemorrhage may occur in the form of punctate extravasations in 
various septic and hemorrhagic diseases, and in parts adjacent to in- 
tense lesions, as in the peritoneum covering the bowel near anthrax 
ulcerations. Hemorrhagic extravasations may likewise be due to 
intense passive congestion, as in death from suffocation or in obstruc- 
tions of the portal circulation. Certain forms of intoxication, like 
phosphorus-poisoning, snake-venom, or the like, may occasion petechial 
ecchymosis or large suffusions; and occasionally hemorrhagic extravasa- 
tions are due to embolic occlusion of the mesenteric arteries. Large 
hemorrhagic effusions may occur in the retroperitoneal tissues, espe- 
cially at the root of the mesentery, between the folds of the omentum, 
or elsewhere into the subperitoneal cellular tissues. These, as well as 
hemorrhages into the peritoneal cavity itself, are frequently traumatic 
in origin. Rupture of the spleen, of the liver, of the uterus or Fallopian 
tubes, or of aneurysms or superficial blood-vessels may be the immediate 
source of large hemorrhages. 

The extravasated blood within the cellular tissues undergoes gradual 
absorption, as elsewhere, and may leave pigmented areas and fibrous 
thickening. The blood within the cavity of the peritoneum may be 



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A TEXT-BOOK OF PATHOLOGY 



directly absorbed, or may be gradually removed after clotting by de- 
generative processes and absorption through the lymphatic channels. 
Inflammatory reaction is wanting unless the blood mass is infected. 
Besides transudates, now to be described, air or bile may be found 
within the peritoneum, almost always resulting from rupture of some 
viscus. Gas, on rare occasions, is produced by some micro-organism. 

Dropsy of the peritoneum, or ascites, may occur as a part of a 
general anasarca in cardiac or renal disease, or may be due to obstruc- 
tion of the portal circulation, notably by cirrhosis of the liver. In these 
cases ascites may be absent at first from the freedom of the collateral 
circulation established between the branches of the inferior and supe- 
rior vena cava and the peripheral radicles of the portal circulation. 
Eventually, however, ascites ensues. In the earliest stages of certain 
cases of intense acute peritonitis and in chronic peritonitis, especially 
the tuberculous form, when the absorption of liquid from the perito- 
neum is disturbed by occlusion of the lymphatics, the liquid effusion 
may have a serous and not the ordinary inflammatory character. 
Chronic peritonitis plays a part in the etiology of many cases of ascites 
ordinarily regarded as the result of obstruction of the circulation alone, 
as in cases of cirrhosis of the liver. In such cases the venous stasis 
may occasion no dropsical exudation until a low-grade chronic peritonitis 
has developed, when the membrane becomes more permeable and 
effusion results. 

An occasional cause of ascites is obstruction of the thoracic duct 
by new growths of its walls, thrombosis within, or pressure from the 
outside. The ascitic liquid in such cases frequently has a chylous char- 
acter. Solid tumors of the ovary are commonly associated with ascites. 

The abdomen in ascites is filled with clear watery or yellowish 
liquid. Gelatinous masses (coagulated serum) often form in the de- 
pendent parts, as in the pelvis and iliac fossae. Occasionally the liquid 
is quite hemorrhagic; in other cases it is milky from admixture of chyle 
or lymph {chylous ascites). The latter cases are dependent upon ob- 
struction or rupture of the lymphatic channels. In other cases, espe- 
cially in instances of endothelioma or carcinoma of the peritoneum, the 
liquid has a milky character from admixture of degenerated cells and 
fatty matter. The term chyliform ascites is sometimes applied to such 
cases. Microscopically, the liquid of ordinary ascites shows red and 
white blood-corpuscles and occasionally a few endothelial cells. In 
the hemorrhagic cases the number of blood-corpuscles is notably in- 
creased, while in chylous ascites there are fat-droplets and granular 
cells. 

Occasionally collections of dropsical liquid occur between the layers 
of the omentum (hydrops omenti). 

Ascites causes more or less serious compression and displacement of 
the abdominal organs. The respirations may be greatly embarrassed 
by upward displacement of the diaphragm, and the circulation may be 
obstructed by the pressure of the liquid upon the veins. Secondary 
changes in the peritoneum are not unusual. Long-standing ascites 



DISEASES OF THE GASTROINTESTINAL TRACT 



693 



nearly always gives rise to a certain amount of chronic inflammation 
(fibrous thickening of the membrane), and terminal tuberculous infec- 
tion of the peritoneum is not infrequent. 

INFLAMMATIONS 

Inflammation of the peritoneum, or peritonitis, is the most im- 
portant condition of this structure. Acute and chronic cases may be 
distinguished. The latter, in most instances, merely represent terminal 
conditions following acute forms of the disease. Exceptionally, peri- 
tonitis may be a chronic affection from the beginning. 

Etiology. — Acute peritonitis is probably always caused by bac- 
teria or bacterial products. It is possible to produce it in animals by 
injections of chemical poisons into the peritoneum, but it is doubtful 
if spontaneous peritonitis ever occurs excepting as a result of infection. 

The bacteria gain access to the peritoneum through the blood, by 
direct migration from the Fallopian tubes, by invasion through the walls 
of the abdominal viscera, or by perforation of the viscera or external 
abdominal walls. Hematogenic peritonitis is sometimes met with in 
cases of general septicemia and pyemia, as in osteomyelitis or malignant 
endocarditis, but such cases are rare. In these instances the bacteria 
may be discharged into the peritoneal cavity from the blood, and may 
thus occasion a direct or primary peritonitis; more frequently a localized 
lesion, such as' a suppurating infarction, is first produced, and the peri- 
tonitis results secondarily from this. Undoubtedly, bacteria are often set 
free in the peritoneum in the course of infections, but this structure seems 
to have a high degree of resistance, and seems to be possessed of special 
means of defence. The experiments of Pfeiffer with regard to the mech- 
anism of immunity (see p. 257) may be cited in this connection. (See 
also note on etiology of pleurisy, p. 587, referable to serous membrane 
defenses.) Idiopathic peritonitis was a term used by older authors to 
designate forms of seemingly causeless peritonitis, or such as follow 
exposure to cold and the like. At the present time we must regard 
these as exceptional instances of primary hematogenic peritonitis or,, 
more commonly, as cases of secondary peritonitis resulting from abdom- 
inal infections that have been overlooked. 

Peritonitis resulting from direct extension of infective processes is 
very common. A certain amount of irritation of the serous coat (the 
peritoneum) of the abdominal organs occurs in most of the diseases 
of these organs, and in the case of certain infectious diseases this may 
attain considerable intensity. For example, in cases of ulcers of the in- 
testines or strangulation of a coil of intestine with secondary necrosis, 
considerable peritonitis, local and eventually general, may occur with- 
out perforation of the gut. In such cases the bacteria penetrate the 
walls of the intestines along the lymphatic channels, and thus reach the 
serous covering. Similar extensions are found in diseases of the tubes 
and ovaries, or of the uterus in puerperal sepsis. 

Perforative peritonitis is the most important of the forms. It may 



694 



A TEXT-BOOK OF PATHOLOGY 



result from perforation of gastric ulcers or cancer, from traumatic or 
ulcerative perforations of other parts of the intestinal tract, from per- 
foration of the appendix in acute appendicitis, or from rupture of dis- 
eased Fallopian tubes; less commonly perforation of the other ab- 
dominal viscera, or rupture of infective foci, such as abscesses of the 
spleen, liver, pancreas, ovaries, or other structures, or penetration of the 
abdomen from without by stab-wounds or disease, may lead to peri- 
toneal infection. 

Among the micro-organisms that have been detected, the Strepto- 
coccus pyogenes is most important, and is the cause of the severest forms 
of peritonitis, such as those occurring in puerperal sepsis. Occasionally 
the disease is due to the Staphylococcus pyogenes, the Bacillus coli com- 
munis, the Diplococcus pneumonia, the bacillus of Friedldnder, the gono- 
coccus, or other organisms. The Bacillus coli is mainly operative in 
peritonitis secondary to intestinal diseases, such as appendicitis. Very 
often, no doubt, peritonitis is the consequence of mixed infection. 

Pathological Anatomy. — Localized and general peritonitis may be 
distinguished. 

Acute localized peritonitis is seen in cases in which bacteria escape 
gradually and in small numbers through the walls of the viscera, 
or in instances in which perforation takes place after exudate has 
formed a wall capable of limiting the extension of the infection. Lo- 
calized peritonitis is most frequent in the' pelvis in association with 
diseases of the tubes or uterus, and in the region of the appendix. 
The peritoneum in the area of disease first becomes intensely injected 
(congested), and the normal luster disappears in consequence of the be- 
ginning exudation and disease of the lining endothelium. Subsequently 
the amount of exudate increases. It may, first, be of serous character, 
but usually is largely fibrinous, and the amount may be considerable. 
Thus, the appendix is not rarely surrounded by masses of fibrinous exu- 
date a centimeter or two in thickness. The exudate may remain fibrin- 
ous, but more frequently becomes fibrinopurulent in the later stages; 
and in cases of perforative peritonitis localized abscesses are com- 
monly met with. In such cases, if the disease remains well encapsulated 
and the patient survives, the exudate may be removed in several ways. 
Very rarely the pus burrows toward the exterior and discharges; more 
frequently it empties into the intestine or some other hollow viscus. 
It may decrease by gradual inspissation, leaving a dry, cheesy mass, 
which in rare instances finally becomes calcareous. Fibrinous exudates 
in localized peritonitis are frequently absorbed, and give place to fibrous 
adhesions. 

Acute general peritonitis may be the immediate result of the dis- 
charge of large quantities of infective matter from a perforated bowel 
or other organ; or it may occur secondarily to a localized peritonitis 
when the limiting wall of exudation is broken down. In these cases 
the peritoneal covering of the intestines, and to a less extent the parietal 
peritoneum, become congested and lusterless, as in the localized form. 
Serous exudation takes place, and may be considerable in amount in 



DISEASES OP THE GASTROINTESTINAL TRACT 



695 



some of the most violent forms of the disease. Acute inflammatory 
ascites is thus produced. Usually, however, the serous exudation is 
scanty, and very soon the intestines are covered with flakes or thin 
coatings of fibrinous exudate and are matted together. Subsequently 
the exudate grows more yellowish from the emigration of leukocytes or 
pus-cells. When adjacent coils of intestine are agglutinated by the 
exudate, pockets containing serous or seropurulent liquid may be formed 
between them. 

In the most virulent forms of peritonitis, local or general, such 
as those due to strangulation and gangrene of a part of the bowel, or to 
puerperal sepsis, the exudates may rapidly assume a putrid character, 
and the deposit upon the serous surface, as well as the serosa itself, 
may undergo necrotic change. In these cases the cavity of the perito- 
neum contains more or less ill-smelling brownish, grayish, or blood- 
tinged liquid exudate, and the affected areas of the peritoneum are cov- 
ered with greenish or brownish deposits. 

Hemorrhagic peritonitis is sometimes observed. It represents 
no special form, but merely indicates systemic or local conditions, as a 
result of which hemorrhagic extravasation has taken place into the 
exudate. This is found in the peritonitis of scorbutic individuals or of 
persons reduced in vitality by other diseases. It also occurs when 
passive congestion is associated with peritonitis, as in cases of cirrhosis 
of the liver. The peritonitis accompanying tuberculosis, and especially 
carcinoma of the peritoneum, may present hemorrhagic exudate. 

Effects of Acute Peritonitis. — The disease of the peritoneum has 
an immediate and profound effect upon the intestines, and reflexly 
or in other ways upon the general system. The peristalsis of the bowel 
in the earlier stages is arrested by spasmodic contraction. Very soon 
the musculature is paralyzed and more obstinate constipation results. 
The systemic effects are most strikingly evidenced by the intense 
shock of the early stages. General septicemia may be the consequence 
of the infective conditions of the peritoneum. 

Chronic peritonitis may be the termination of an acute peritonitis, 
especially the localized form. In other cases chronic inflammatory 
thickening occurs in the peritoneum adjacent to or covering organs 
the seat of various diseases. Thus, in cirrhosis of the liver the peritoneal 
covering and the reflexions forming the ligaments may be greatly thick- 
ened, and similarly the peritoneum covering the spleen may be involved 
in consequence of chronic congestion or inflammation of this organ. 
These adhesions may distort organs or act as bands to constrict the 
intestines, under which circumstances intestinal obstruction may arise. 
When adhesions are numerous, peristalsis is embarrassed and constipa- 
tion is common. 

Chronic peritonitis following local acute peritonitis usually presents 
itself in the form of fibrous thickenings or adhesions, such as are so often 
encountered in the pelvis after uterine, tubal, or ovarian disease com- 
plicated by peritonitis, and about the appendix after inflammations of 
this structure. Less commonly chronic peritonitis is met with in the 



696 



A TEXT-BOOK OF PATHOLOGY 



form of sacculated effusions. In such instances the effusion formed dur- 
ing the acute stage is only partially absorbed, and remains as an in- 
spissated liquid. 

In other cases dense adhesions are formed, and occasionally cal- 
careous plates are found in the thickened peritoneal covering of the 
bowels or other parts. The omentum aids in localizing peritonitis, es- 
pecially of the acute exudative forms, and is actively included in the 
chronic stages. It is also a source from which blood and cellular ele- 
ments come into the cavity of the peritoneum, since it is more vascular 
than the rest of the membrane. 

Chronic diffuse peritonitis may result from diffuse acute peritonitis. 
In such cases there are widespread adhesions, and the peritoneum is 
more or less diffusely thickened. Considerable liquid effusion may be 
present. In other instances diffuse peritonitis arises in an insidious 
manner as a chronic process from the beginning. Some of these cases 
are entirely obscure in etiology; in a few it has seemed probable that 
syphilis was an etiological factor. The peritoneum is often uniformly 
thickened, but in some cases presents small nodular lesions, suggesting 
miliary tubercles. In several instances these nodules, together with the 
abundant serous effusion occasionally met with, have led to the diag- 
nosis of tuberculous peritonitis. Microscopical examination of the 
nodules, however, shows a fibrous structure, and .neither giant cells 
nor tubercle bacilli. Tuberculous and malignant peritonitis will be 
considered below. 

Hyperplastic Perihepatitis. — A few cases have been observed of a 
remarkable disease in which the upper part of the parietal peritoneum 
and the reflexions covering the liver and spleen are greatly thickened 
and of dense sclerotic character — hyaloserositis. The peritoneum is 
sometimes several millimeters in thickness, gray or white, and suggests 
the appearance of the "icing" of confectioners. This has led to the 
term proposed by Curschmann — Zuckergussleber. The liver and spleen 
undergo more or less pressure-atrophy, and ascites is a frequent symp- 
tom. The etiology is obscure. 

INFECTIOUS DISEASES 

Tuberculosis may in rare instances affect the peritoneum primarily, 
as in cases in which tubercle bacilli penetrate the mucosa of the intes- 
tines and enter the lymphatics without causing an intestinal lesion; 
or in cases of infection through the Fallopian tubes. Usually tubercu- 
losis of the peritoneum is secondary to tuberculosis of some abdominal 
viscus or of more distant organs. Thus, among the more frequent causes 
are tuberculosis of the mesenteric or retroperitoneal glands and tubercu- 
lous disease of the tubes and ovaries in women. Intestinal tuberculosis 
rarely leads to more than localized lesions of the serous coat opposite the 
ulcerations of the mucosa. Pulmonary tuberculosis may occasion hemato- 
genic infection of the peritoneum. Simultaneous tuberculosis of various 
serous membranes, especially the pleura and peritoneum, is occasionally 



DISEASES OF THE GASTROINTESTINAL TRACT 



697 



observed. The source of infection is often hidden; sometimes the 
pleura is first involved and the peritoneum becomes affected by exten- 
sion; less commonly the reverse occurs. 

Pathological Anatomy. — Miliary tuberculosis without marked in- 
flammatory changes may occur as a generalized peritoneal affection 
in acute or subacute general miliary tuberculosis. Local eruptions of 
similar character are seen in the pelvic peritoneum in cases of tubal or 
ovarian tuberculosis and upon the serosa of the intestines adjacent to 
tuberculous ulcers of the bowel (Fig. 323). 




Fig. 323. — Disseminated miliary tuberculosis of peritoneum with caseous glands in the 

mesenteric stalk. 

More important, from a clinical point of view, are the cases in 
which inflammatory changes are associated with the specific tubercle. In 
some instances unaccompanied by a fluid exudate extensive adhesions 
by fibrinous or fibrous productions are met with, while the tubercles 
tend to agglutinate, forming masses of considerable size and of cheesy 
character. The mesenteric lymph-glands may be coincidently involved, 
being enlarged and caseous. Sacculated collections of serous or sero- 
purulent liquid are sometimes observed. In another variety there is 
abundant serous exudation. Occasionally the exudate is hemorrhagic. 

Tuberculosis of the peritoneum sometimes terminates in com- 
plete resolution, the peritoneum being left somewhat thickened, but 
showing no other evidences of the previous disease. 



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A TEXT-BOOK OF PATHOLOGY 



TUMORS 

Fibromata and lipomata are sometimes met with as small nodular 

or pedunculated outgrowths from the subperitoneal tissues. 

Sarcoma may occur in the form of diffuse gelatinous tumors of 
angiosarcomatous structure, or in the form of endotheliomata. The 
latter variety occasions diffuse thickening, sometimes of considerable 
areas, of the peritoneum. Secondary sarcoma is sometimes observed 
as nodules of considerable size or as numerous miliary nodules. 

Carcinoma of the peritoneum is secondary. Gelatinous or colloid 
cancers of the stomach and bowel (rectum) frequently extend widely 
through the peritoneum, causing great thickening and a remarkably 
gelatinous growth. Not rarely rounded masses of pearly appearance are 
observed (see Fig. 91). In rare instances tumors of the peritoneum of 
the same general character seem to be primary, and the reasonable ex- 
planation has been suggested that parts of intestinal tissue, pinched off 
in fetal development, are the starting-points of the growths. Secondary 
cancer frequently appears in the form of nodular tumors in association 
with ovarian cystomata that have become carcinomatous, or with 
primary cancers of the ovaries and other pelvic organs. Thus arises 
the 'pseudomyxoma peritonei, a name applied because of the tendency 
to myxomatous degeneration shown by tumors of the peritoneum aris- 
ing by continuity. The cystadenomata of the ovary seems to be able 
to grow on peritoneal surfaces after the primary tumor has ruptured. 
Occasionally widespread eruption of miliary nodules is met with as a 
part of acute carcinomatosis. 

In all forms of carcinoma of the peritoneum inflammatory changes 
with intestinal agglutination and adhesion are frequent. Hemorrhagic 
exudation is not unusual. In rare cases the bowels are so firmly fused 
by the spreading tumor and the inflammatory exudates that they form 
a solid mass, which on section shows the cavities of adjacent coils of 
intestines separated by more or less uniform tumor tissue. 

Lymphcysts are occasionally found beneath the peritoneal surface 
and in the mesenteries. 

PARASITES 

Echinococcus cysts occasionally occupy the peritoneal cavity, and 
may fill it almost completely. Filaria have been found in a few in- 
stances ; and the Linguatula rhinaria and Cysticercus cellulosce have been 
reported. An ameboid organism (Leydenia gemmipara) has been dis- 
covered in the liquid exudate of certain cases of ascites. 



CHAPTER VI 



DISEASES OF THE DUCTLESS GLANDS 
The Thyroid Gland 

Anatomical Considerations. — The thyroid gland is a compound 
tubular gland, which in fetal life communicates with the pharynx at the 
base of the tongue by a duct. Later the duct is obliterated, and the 
gland becomes ductless. Microscopically, there are found acini lined 
with polyhedral or cylindrical epithelium, usually in a single layer. 
The lumen of the acinus contains more or less gelatinous or, as it is 
usually called, colloid material, which seems to be a secretion of the 
epithelium. It is composed of nucleoprotein and globulin, the latter, 
the thyreoglobulin, containing a notable proportion of iodin. The vascu- 
lar supply of the gland is very abundant, the blood-vessels being numer- 
ous and the anastomoses very free. The lymphatic network is equally 
abundant, and mainly situated in the stroma of the gland around the 
acini. The larger lymphatics are supplied with valves like those of the 
veins. Occasionally colloid material has been found in the stroma and 
in the lymphatics. The capsule of the gland is a fibrous covering from 
which trabeculee extend into the substance of the organ. 

CONGENITAL DEFECTS 

Occasionally one or another part of the gland is wanting, or, in rare 
instances, the entire organ. 

Accessory thyroid glands have been found in various situations. 
Sometimes small masses of thyroid tissue occur alongside of a normal 
gland, either above it, in the neck; or below it, behind the sternum and 
in the anterior mediastinum. In other cases the normal thyroid is ab- 
sent, but is represented by small masses in the situations named or in 
other parts. In a few instances tumors at the base of the tongue and 
within the larynx and traches have been found to be composed of thyroid 
tissue, or the thyroglossal duct remains partly patulous and cyst-like 
swellings arise. 

DISTURBANCES OF CIRCULATION 

Hyperemia of the thyroid gland is met with very frequently. It 
occurs in cases of cardiac failure, and in consequence of obstruction 
of the large veins by mediastinal tumors and the like. In these in- 
stances the thyroid may be considerably enlarged, and has a soft, 
doughy character. Slight enlargement of the thyroid of congestive 
character is found in perhaps a majority of the cases of chlorosis, and 

699 



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A TEXT-BOOK OF PATHOLOGY 



may be present in any form of anemia and during pregnancy and men- 
struation. In Graves' disease the thyroid may be very vascular, and 
the enlargement of the gland may be in large part due to dilatation of 
the blood-vessels (see below). 

INFLAMMATIONS 

Acute thyroiditis may occur in the course of various infectious 
diseases, notably typhoid fever. Occasionally it arises without definite 
preceding disease. The gland enlarges and becomes rather tense. The 
termination is usually in resolution, and this may occur very rapidly, 
suggesting that the enlargement of the gland is due largely to con- 
gestion and liquid exudation, rather than to cellular (inflammatory) 
infiltration. 

Acute suppurative thyroiditis, or abscess, occurs in consequence 
of embolism, in cases of infected wounds, endocarditis, or general pye- 
mia. Sometimes the inflammation extends directly from local diseases, 
such as diphtheria. The abscess may rupture, or may undergo secondary 
changes — inspissation, calcification. 

STRUMA OR GOITER 

Definition. — Goiter is the name applied to various enlargements 
of the thyroid gland. It is a clinical rather than a pathological term. 
Sometimes a distinction is made between benign and malignant struma, 
the latter term including definite tumors of the thyroid gland. At the 
present time the term "goiter" is restricted to enlargements of a hyper- 
plastic character, which, though often resembling tumors, cannot be 
definitely classified among the tumors of the gland. 

Etiology. — Goiter occurs endemically in certain situations, as in 
Switzerland and other parts of Europe, and in various parts of this 
country. Sporadically, it is met with in all parts of the world. Local 
conditions of some kind are doubtless among the fundamental causes, 
but the nature of these conditions is but little known. The drinking- 
water has always been suspected, and it seems likely that it has some 
influence, though it is certain that the magnesium and calcium salts 
have not the importance formerly ascribed to them. Infectious causes 
have been suspected and micro-organisms have actually been described, 
but no satisfactory demonstrations have been made. 

Pathological Anatomy. — Two principal varieties may be distin- 
guished: the parenchymatous and the vascular. 

Parenchymatous goiter is a variety in which the glandular tissues or 
acini undergo more or less active hyperplasia. The gland is generally 
uniformly enlarged, but sometimes presents lobular or nodular eleva- 
tions. The tissue is ordinarily somewhat elastic, like that of the normal 
thyroid, but may in other instances.be very firm. Occasionally cystic 
forms occur, and a subvariety is sometimes distinguished by the term 
cystic goiter. 



DISEASES OF THE DUCTLESS GLANDS 



701 



Microscopically, there may be found merely a uniform hyperplasia 
of the glandular acini, without any notable change in the structure of 
the tissue. The hyperplasia may be so great as to simulate papillary 
cystadenoma (see Fig. 326). In most instances the acini contain but 
small quantities of colloid material, as is the case in the normal gland. 
Sometimes, however, there is abundant production of colloid, and the 
acini are greatly distended; the term colloid goiter may be applied in such 
instances (Fig. 324) . In certain cases the walls of the acini are destroyed 
and the colloid of adjacent acini runs together, forming considerable cysts. 
In these instances the thyroid consists of numerous cystic excavations. 




Fig. 324. — Colloid goiter, showing colloid material in the dilated acini. 



Changes in the interstitial connective tissue of the gland may be com- 
paratively slight, but may in other cases become conspicuous. The 
capsule of the gland may be thickened, and the stroma may predominate 
over the glandular elements. The term fibrous goiter has been suggested 
for such cases. 

Vascular Goiter. — This term is applied to enlargements of the 
thyroid gland characterized by marked dilatation of blood-vessels within 
the organ. The glandular tissues themselves present changes similar 
to those described under Parenchymatous Goiter. The gland undergoes 
considerable and sometimes enormous enlargement, and may pulsate 



702 



A TEXT-BOOK OF PATHOLOGY 



actively. This form of goiter is met with as the important pathological 
condition of many cases of Graves' disease (see p. 707). 

The alveoli vary greatly in size and form, often sending out diver- 
ticula which become constricted off to form new alveoli (Fig. 325). 
The epithelium is at first hyperplastic, then becomes flatter as the col- 
loid increases in amount and density. The vascular supply is unusually 
rich, the veins especially being large and distended with blood, their 
walls being very friable. They lie, for the most part, in the increased 
connective-tissue framework, in which tissue are also numerous small, 




Fig. 325. — Parenchymatous and vascular goiter, showing large, thick-walled blood-vessels. 

circumscribed, scattered lymphoid nodules. Corresponding with this 
there is an enlargement of the cervical lymph-glands and of the thymus. 

The parathyroid glands show a moderate atrophy of cells and 
induration or increase of connective tissue, but this is by no means con- 
stant or sufficiently extensive to support the idea that these glands are 
in any way the cause of the disease. 

There is also recognized a form of goiter in which hyperplasia, in- 
stead of being diffuse as in the two preceding types, is of a nodular 
character. In this case areas of active hyperplasia are mixed with 
normal or atrophic fields. To these cases the name adenomatous goiter 
is given. If, however, the lobular and acinus grouping should revert 



DISEASES OF THE DUCTLESS GLANDS 



703 



to the fetal character, the name fetal adenoma is given (Fig. 327). It 
must be emphasized that these are not tumors, as their names would 
imply, but hyperplasias of insular character whose causation is not 
understood. They are actively proliferative forms, especially the latter, 
but may or may not give symptoms. 

Relation of Histological Change to Clinical Conditions. — The func- 
tion of the thyroid cells seems to be to form colloid and elaborate an 
internal secretion, the latter seemingly closely bound with the former. 
The resting gland has low cuboidal or thick flat cells, a moderate amount 
of colloid, little interstitial cellular content, and moderate vascularity. 
With hyperplasia first comes congestion, then increase in the size of the 
epithelium and reduction of colloid, for, with greater blood-supply, 




Fig. 326. — Papillary cyst adenomatous hyperplasia of thyroid gland. 

more absorption takes place. This, in any one of the anatomical forms 
of hyperplasia mentioned above, supplies the basis for hyperthyroidism. 
As the vascularity and, usually, interstitial cellular infiltrate increase, 
low-grade inflammatory changes may take place and a stage of retro- 
gression set in. This is marked by a lower stature of the epithelium, 
firm colloid and fibrous tissue increase. There is less absorption at this 
stage, and it represents a condition possible in simple goiter. A return 
of hyperplasia in such an atrophic gland may again lead to toxic symp- 
toms. It seems that the absorption of colloid is responsible for hyper- 
thyroidism. The iodin content of fully formed colloid in normal or 
regressive thyroids is high, while that of the mucoid material replacing 
colloid in hyperplastic glands is low. What disturbs the balance and 
induces the hyperplasia is not known. 



704 



A TEXT-BOOK OF PATHOLOGY 



Secondary Changes. — The hyperplasia of connective tissue between 
the acini has been referred to. Sometimes this becomes so considerable 
that the term "fibrous goiter" is warranted. Cystic formations have 
also been mentioned, the cysts referred to resulting from the confluence 
of the dilated acini. The contents in such cases consist of colloid 
material or of more or less serous or hemorrhagic liquid. Occasionally 
cysts result from hemorrhage in degenerated parts of the gland, with 
subsequent absorption of the blood and exudation of serous liquid. 
The contents in such cases may be purely serous or may consist of 
brownish grumous matter containing abundant cholesterol. Very rarely 
secondary proliferative changes occur in the walls of the cyst, causing 




Fig. 327. — Fetal adenoma of thyroid. 



papillomatous projections. Calcification is a very common terminal 
change in degenerated goiters. It may occur in isolated areas or may 
cause a uniform hardening of the gland. Actual ossification has been 
observed. Inflammation of a goitrous thyroid is known as strumitis, 
to distinguish it from thyroiditis. 

Mechanical Effects of Goiter. — The enlarged gland presses upon 
the adjacent structures more or less seriously. The trachea is most 
frequently compressed or dislocated from its median position. Pressure 
upon the large veins may occasion passive congestion and edema; and 
less commonly pressure on the carotid artery may interfere with the 
circulation of blood in the brain. The nerves in the vicinity (vagus, 
recurrent laryngeal, and sympathetic) are likewise exposed to pressure. 



DISEASES OF THE DUCTLESS GLANDS 



705 



INFECTIOUS DISEASES 

Tuberculosis may occur in the form of miliary tubercles or as small 
caseous nodules. 

Syphilis is met with in the form of gummata. 
Actinomycosis is a very rare disease of the thyroid gland. 

TUMORS AND PARASITES 

Tumors. — The term "malignant struma" is sometimes applied to 
tumors, and it is difficult in certain cases to draw a sharp line between 
certain goiters and distinct new growths (adenomata). 

All tumors of the thyroid have a tendency to cystic change and, as 
might be expected of this organ, to collections of colloid. These charac- 
teristics persist in metastases. 

The term adenoma, however, should be restricted to cases in which 
the proliferation of acini is atypical, and in which the tumor is circum- 
scribed, nodular, or otherwise distinguishable from the pre-existing 
gland tissue. Sometimes tumors of the thyroid having typically adeno- 
matous characters give metastasis. The tumors are prone to assume 
cystic and papillomatous change. 

Carcinoma may occur in the form of a nodular or more diffuse tumor. 
Metastasis is frequent in cases of carcinoma, but also occurs in cases that 
present the appearances of an ordinary adenoma. The bones are fre- 
quently involved by metastatic deposits. Extension from the thyroid 
to the adjacent organs is not infrequent. Carcinoma sarcomatodes 
has been described several times. 

Sarcoma occurs in several varieties. Round-celled sarcoma and 
angiosarcoma are particularly malignant. 

Secondary tumors in the thyroid are rare. 

Parasites. — Echinococcus cysts have been met with, but are very 
rare. 

GENERAL RESULTS OF THYROID DISEASE 

The physiology of the gland has not as yet been fully determined, 
though certain facts have become established. The old authors be- 
lieved the gland to be active as a blood-making organ, and this is still 
maintained by some. It is, however, unlikely that this function is an 
important one. The frequent association of thyroid disease with certain 
general conditions (cretinism and myxedema) has led to experiments 
upon animals that have established certain important facts. 

In earlier experiments at removal of the thyroid gland in animals 
various nervous symptoms resembling those of tetany were noted. 
Later investigations have shown that these results were due to the 
simultaneous removal of the parathyroid bodies. In more recent 
studies care has been taken to avoid this parathyroid ablation, and it 
has been found that in young animals checking of ossification and 
stunting of growth, enlargement of the hypophysis, apathy, and other 

45 



706 



A TEXT-BOOK OF PATHOLOGY 



symptoms suggestive of cretinism in man occur. In adult animals 
typical cachexia strumipriva results. This is characterized by pallor, 
edema of the skin, general weakness, loss of hair, and alteration of the 
cerebral functions (intellection, sensation, and motor power). 

Removal of the thyroid causes a decrease in protein metabolism and 
an increased tolerance of carbohydrates without the production of 
glycosuria. The latter effect seems to be due to an action of the thyroid 
antagonistic to that of the pancreas which checks the mobilization 
of sugar, while the thyroid facilitates it. 

Cretinism is a peculiar disease, oc- 
curring with great frequency in certain 
parts of central Europe, especially in 
Switzerland, and not infrequently in 
other parts of the world. The thyroid 
gland is sometimes atrophic and some- 
times goiterous, but in all cases diseased. 
The disease is not, as a rule, present at 
birth, but usually develops soon there- 
after; the parents may be cretinoid or 
goiterous, though sometimes healthy 
parents have cretin children. The cretin 
remains physically and mentally unde- 
veloped; the subcutaneous tissue is flabby, 
abundant, and sometimes distinctly myx- 
edematous (Fig. 328); the head is large; 
the lips and tongue thickened, and the 
latter often protrudes from the mouth; 
the hairs of the body are little developed. 
Lack of bony development and incom- 
plete ossification occasion the stunted 
and often deformed condition of the 
cretin. 

A distinction must be made between 
sporadic and endemic cretinism. In the 
latter the appearances are much less uniform and the mental retarda- 
tion comparatively more marked than the physical evidences of 
cretinism. 

Myxedema is a disease that develops in later life, sometimes after 
distinct diseases of the thyroid (goiter, gumma, tumors, etc.), but 
often without any manifest disease of thyroid, though atrophy and de- 
generations (calcification) may be disclosed by the postmortem ex- 
amination. There is a peculiar swelling of the eyelids and of the sub- 
cutaneous tissue of the face and neck, and subsequently the same change 
occurs elsewhere, involving the limbs and the entire body. The appear- 
ances at first suggest edema, but there is not the usual pitting on pres- 
sure, and the feeling conveyed to the hand is that of an infiltration with 
some form of gelatinous tissue. This has been found to consist of a 
mucin-like substance, often associated with increase of the adipose tissue 




Fig. 328.— Cretin. 



DISEASES OF THE DUCTLESS GLANDS 



707 



itself. The skin of the patient is pallid and exceedingly dry; the hair 
falls out, and nervous symptoms are developed. Eventually, intellec- 
tion may be almost destroyed. 

The resemblance of these diseases to the symptoms produced by 
operative removal of the thyroid gland makes it certain that disease 
of the thyroid is the fundamental condition in cretinism and myxedema. 
This fact is still more clearly demonstrated by the numerous cures of 
these diseases following implantation of sheeps' thyroids in the perito- 
neal cavity, and especially the feeding of thyroid-gland tissue or ex- 
tracts. 

Graves' disease has been referred to in connection with goiter. 
The cardinal symptoms of this disease are enlargement of the gland, 
palpitation of the heart, exophthalmos, and muscular tremor. The 
pathology of the disease has not as yet been fully determined. It 
seems likely, however, from recent investigations that the thyroid dis- 
ease, from whatever cause it may 
result, is the primary disorder. 
Removal of large parts of the 
gland has been found to control 
the symptoms of Graves' disease 
in a large number of cases, and 
the feeding of thyroid extract for 
a long period of time produces 
symptoms like those of Graves' 
disease: rapid action and palpi- 
tation of the heart, exophthalmos, 
and tremor. According to the 
view here expressed, the symp- 
toms which together constitute 
Graves' disease are probably due 
to overproduction of thyroid se- 
cretion; they are, in fact, the re- 
sult of hyperthyroidism. While 
the symptoms, pathological an- 
atomy, and chemistry indicate 
too much thyroid, the actual 
state of affairs according to some 
writers is one of thyroid insuffi- 
ciency, in that some normal secre- 
tion is diminished or perverted. 
It seems possible to have Graves' 

disease without great alterations in the anatomy of the gland, at the 
time seen at least. The opinion, however, is held by others that Graves' 
disease is primarily an affection of the nervous system. 

The parathyroid glands are small bodies lying on or within the 
capsule of the thyroid, consisting of closely packed acini similar in 
cellular appearance to the larger gland in its fetal stage. The number 
varies from one to six. Their relation to the thyroids and general 




Fig. 329. — The thyroid gland and para- 
thyroid glandules; blood-suppy (posterior 
view) (Halsted and Evans). 



708 



A TEXT-BOOK OF PATHOLOGY 



metabolism is not clearly understood. Their complete removal seems 
to cause tetany. That they have some importance in the calcium 
metabolism and that this latter stands in some relation to tetany is in- 
dicated by a disappearance of tetany upon the introduction of calcium 
salts. In some way these glands regulate the deposit of calcium salts 
in bone. The parathyroids are sometimes the seat of hyperplasia or 
true tumors. 

The Suprarenal Bodies 

Anatomical Considerations. — The suprarenal bodies are com- 
posed of a cortical and a medullary portion, and are enclosed in a 
fibrous capsule from which septa extend into the substance of the 
organ. The cortical portion is composed of columns of polygonal 
cells filled with doubly refractive granules of lipoid substance. 
Three layers are distinguishable in the cortex: an outer zone, in which 
the cells are arranged in oval masses (zona glomerulosa) ; a middle 
zone, in which they form cylindrical columns extending toward the 
medulla {zona fasciculata) ; and an inner zone, composed of irregularly 
anastomosing columns of cells (zona reticularis) . The cells of the middle 
zone are the most markedly granular. The medulla of the gland consists 
of similar polygonal cells arranged in cords or irregularly anastomosing 
columns, and contains numerous non-medullated nerve-fibers and mul- 
tipolar nerve-cells, as well as aggregations of cells which are stained 
brown by chromic acid (chromaffin cells). These cells are derived from 
the neuroblasts of the central nervous system and are found distributed 
in various situations as a "chromaffin system." Among these situations 
are the sympathetic nerves, the root of carotid arteries, the left coronary, 
the superior mesenteric, the solar plexus, etc. In all these situations 
the chromaffin cells doubtless have the same functional action — manu- 
facture of adrenalin or epinephrin — as in the suprarenal bodies. 

Physiological Functions. — The important function of the supra- 
renal gland, thus far determined, is the manufacture of epinephrin by the 
chromaffin cells. This substance has the general effect of stimulating the 
peripheral ends of the nerves of the true sympathetic system, owing to 
which it causes marked rise of blood-pressure. Probably the same 
action accounts for the occurrence of glycosuria following injections of 
epinephrin, the action in this case being upon sympathetic nerve-fibers 
in the liver. This and other evidence indicates that the suprarenal 
glands are closely related to carbohydrate metabolism. It is believed 
that epinephrin is diminished in nervous strain, fatigue, injury with 
shock, and bacterial diseases. While it is supposed to be increased in 
conditions with high blood-pressure, there is no proof that this secre- 
tion is high in any disease. 

The occurrence of pigmentation in Addison's disease suggests a 
relationship of the suprarenal glands to the pigment production, but the 
pathogenesis is not as yet clearly determined. 



DISEASES OF THE DUCTLESS GLANDS 



709 



CONGENITAL ANOMALIES 

Accessory suprarenal bodies may be found in the vicinity of the ■ 
main body. Of peculiar interest are the portions of suprarenal tissue 
(cortical cells) found in the capsule or cortex of the kidney. These "rests" 
may subsequently proliferate and form tumors of the kidney. (See 
Tumors of the Kidney.) 

Occasionally the suprarenal bodies are found in unusual situations. 

Malformations of the adrenal system seem to be connected with 
similar changes in the nervous and genital organs. 

DEGENERATIONS 

Fatty degeneration is normal in adults. It affects the cortex, giving 
this layer a yellowish color. The substance of the cortex may separate 
through the middle zone, forming a cavity suggesting a cyst. This is 
probably in part a postmortem production. 

Pigmentation is observed in the cells of the medullary portion, 
especially in persons of advanced age. 

Amyloid infiltration occurs in connection with amyloid disease of 
other organs. The suprarenal body becomes hard and of a grayish, 
translucent appearance. The degeneration affects the walls of the 
blood-vessels, from which it extends to the connective tissue. The 
glandular portions suffer pressure-atrophy. The cortex is more fre- 
quently involved than the medulla. 

INFECTIOUS DISEASES 

Tuberculosis of the suprarenal body is the most important of its 
diseases. Miliary tubercles may be met with in cases of general tuber- 
culosis, but a fibrocaseoits form of the disease is more frequent and of 
much greater significance. The gland is enlarged, sometimes reaching the 
size of an egg; it is hard and usually rather nodular or irregular in out- 
line. The capsule is thickened, and the substance of the gland is com- 
posed of dry, yellowish, cheesy matter, or of a puriform material. 
In the later stages the caseous or puriform matter may be inspis- 
sated, and fibrous-tissue growth may convert the entire body into 
a shrivelled, hard mass of connective tissue. Sometimes one gland 
alone is involved ; more frequently the disease occurs bilaterally. Tuber- 
culosis of this form may be primary, but usually is secondary to tuber-, 
culosis of the lungs, intestines, or other organs. 

Addison's disease, in which fibrocaseous tuberculosis of the supra- 
renal bodies is commonly present, is an affection characterized by 
brownish pigmentation of the skin of exposed parts of the body (face, 
neck, and hands), and of the skin in the flexures of the joints or in other 
parts subjected to pressure. The pigmentation usually occurs in a 
mottled form at first, but soon becomes uniform. Brownish or purplish 
spots upon the mucous membranes (mouth) are not unusual. Besides 



710 



A TEXT-BOOK OF PATHOLOGY 



pigmentation the characteristic symptoms are great weakness, disturb- 
ances of the stomach (vomiting), and cardiovascular asthenia. 

Though fibrocaseous tuberculosis of the suprarenal gland is dis- 
covered in many cases, Addison's disease may occur in association 
with other affections of the suprarenal, such as tumors; and it may be 
absent despite the existence of tuberculosis or of other diseases of both 
of the glands. The absence of Addison's disease in the latter cases has 
been explained by some writers by the assumption that the suprarenal 
disease had not existed long enough for the development of the symp- 
toms of Addison's disease. Occasionally, alterations in the sympa- 
thetic nervous system (semilunar ganglia and solar plexus) have been 
discovered when the suprarenal glands were apparently normal. No 
explanation of such cases can be made. It must be accepted at the 
present time that the suprarenal bodies are in some way concerned 
in the etiology of the disease, but it is impossible to state how much dis- 
ease of the cortex and medulla (chromaffin system) respectively are 
concerned. It seems evident that the medulla is more largely involved, 
and disease of the chromaffin system outside the adrenals may explain 
the cases of Addison's disease without lesions of these glands. The 
disease of the gland need not, however, be of any special sort. 

Lewin found among 281 cases — typical cases of Addison's disease 
with sound adrenals, 20 per cent. ; typical cases of Addison's disease with 
diseased adrenals, 80 per cent.; disease of adrenals without bronzing, 
28 per cent. ; disease of adrenals with bronzing, 72 per cent. In Addi- 
son's original paper he included 3 cases of secondary cancer of the 
adrenals. 

Tumors and hyperplasia of the adrenal cortex in the young female 
lead to early puberty and a certain degree of masculinity, and in the 
male to general sexual precocity. 

The carotid and coccygeal glands are a part of the system we have 
been discussing, but are of little importance pathologically, aside from 
an occasional tumor beginning in them. They are of glandular structure 
and contain chromaffin cells. 

Syphilis occurs in the form of gummata. Uniform fatty degenera- 
tion of the suprarenal body has been met with in congenital syphilis. 

CIRCULATORY DISTURBANCES 

Hemorrhage is comparatively rare. It may occur in association 
with hemorrhagic diseases or severe anemias, especially leukemia. 
Sometimes it is caused by traumatism or by obstruction of the venous 
circulation. The hemorrhage may be inconsiderable or may be quite 
large. In the latter instances secondary rupture of the hematoma may 
cause death by intraperitoneal hemorrhage or a hemorrhagic cyst 
may result. 



DISEASES OP THE DUCTLESS GLANDS 



711 



INFLAMMATION 

Inflammation of the suprarenal body is very rare. A simple and 
a hemorrhagic form have, however, been described. Abscess may 
occur in consequence of pyemia, or as a secondary condition following 
other forms of suprarenal disease. 

TUMORS 

Sarcoma is the most frequent form of tumor. Melanotic as well as 
unpigmented varieties are met with. The tumor may reach consider- 
able size, and may destroy the gland completely. 

Adenoma may arise from the cells of the acini. Histologically, these 
tumors resemble the fascicular zone of the cortex, from which they 
doubtless arise in the great majority of cases. The tumor occurs 
as a nodular, irregular growth, often of a yellowish or brownish color. 
"Lipomatous struma of the suprarenal" is a name given by Virchow to 
a fatty nodular tumor growing from the cortex. 

Hypernephroma may occur as a primary tumor in the suprarenal, 
and when found in the young is almost always associated with ab- 
normalities of the sexual characters. In the cases of hypernephroma of 
the kidneys these conditions are usually lacking. 

Gliomata have been described, but it is doubtful whether these 
tumors are true gliomata. 

Neuroma is a rare form of suprarenal tumor, arising from the 
neural tissue in the medulla. 

Secondary sarcoma and carcinoma are not infrequent. 

Tumors of the cortex of the kidney, having the structure of supra- 
renal tissue, are described under Tumors of the Kidneys. 

The Thymus Gland 

Anatomy and Development. — The thymus gland at its earliest 
period consists of endodermic epithelium arranged somewhat like that 
of an epithelial gland. Later, mesoblastic lymphoid cells and con- 
nective tissue infiltrate it; and at birth and for several years there- 
after it is composed largely of tissue arranged like the follicles of 
lymphatic glands. It is, however, in no way a lymph organ. Here 
and there in the center of these may be seen concentric whorls (the 
corpuscles of Hassall), the remains of the original epithelial cells. After 
the second year of life retrogressive changes take place, and by the age 
of adolescence the gland is converted into a mass of fatty connective 
tissue. 

Congenital Abnormalities. — Complete absence or various minor 
irregularities of the thymus may occur; at times it is found enormously 
hypertrophied. In the latter case the root of the great vessels, the 
pericardium, and heart may be covered over by the enlarged thymus, 



712 



A TEXT-BOOK OF PATHOLOGY 



and sudden death seems at times due to this cause. The swelling of the 
thymus is a part of the so-called status lymphaticus, and is associated 
with a rapid swelling of all lymphoid tissues. It is noteworthy that 
the medulla of the thymus is hyperplastic, while the cortex is unchanged. 
The cause of the condition and its fatal outcome is unknown. Thymic 
asthma, so-called, is rarely if. ever due to enlargement of the thymus 
and compression by it upon heart or trachea. (See Diseases of the 
Lymphatic Glands.) 

Circulatory Disturbances. — Intense congestion and punctate hem- 
orrhages may be found in cases in which death has occurred from 
asphyxia. 

Inflammation as a primary disease is of doubtful occurrence, but 
abscesses may occur in cases of general pyemia, or from extension of 
suppurative affections of adjacent parts. 

Infectious Diseases. — Syphilis occurs in the form of gummata, 
especially in the newborn. Caseation and softening of the gumma 
may occur, and a resemblance to abscess is thus produced. Miliary 
or caseous tuberculosis occasionally invades the thymus gland. 

Tumors. — The thymus or its remnant is not infrequently the place 
of origin of lymphosarcoma of the anterior mediastinum (see Fig. 58). 
Tumors having this origin may be recognized by their shape and by 
the regularity of their outlines, the lymphosarcomata (lymphadeno- 
mata) of the lymphatic glands of the anterior mediastinum having a 
more irregular tabulated appearance. Ordinary round-celled sarcoma 
has been described, and epithelioma springing from the corpuscles of 
Hassall has been seen in a few cases. Dermoid cysts and angiomata 
have been seen. 

THE PITUITARY BODY, OR HYPOPHYSIS CEREBRI 

The hypophysis is a small glandular organ, situated at the base of 
the brain, lying upon the upper surface of the body of the sphenoid 
bone, and further protected posteriorly by a wall, forming a cavity 
which is known as the sella turcica. It varies slightly in size, the average 
weight in the adult being from 0.59 gm. (Schonemann) to 0.48 gm. 
(Comte). It reaches its maximum between twenty-one and forty years 
of age. 

The hypophysis is a double organ, developed from the central nervous system 
and from the alimentary canal. The nervous part originates from the middle 
primary cerebral vesicle as an evagination from the cavity. This forms the infun- 
dibulum and the small posterior lobe. The larger anterior lobe, or true pituitary 
gland, appears to arise from two sources, one, the primitive oral tissue in early 
embryonal life, and the other the anterior portion of the alimentary canal; both 
portions become contracted at their origins, fuse, and are ultimately separated from 
the alimentary canal, although this separation is not complete in some of the lower 
vertebrata. Histologically, the organ may be divided into three parts : the ante- 
rior portion of the anterior lobe is composed of somewhat polygonal epithelium 
enclosed in alveoli, whose walls are made up of fibrous connective tissue. These 
groups of cells are very irregular, although sometimes they are arranged about the 



DISEASES OP THE DUCTLESS GLANDS 



713 



periphery of the cavity, leaving in the center a small lumen, which, more frequently 
than not, is filled with an oxyphilic homogeneous mass that is supposed to be colloid. 
The amount of connective tissue is usually relatively small, and it contains a con- 
siderable proportion of cells as compared with connective tissues of other parts of 
the body, and is exceedingly vascular. The cells are of two kinds, the chromophilic 
and the chromophobic. The former are further divided by Comte into the eosino- 
philic, in which the protoplasm stains deeply and homogeneously with eosin, and 
usually contains vacuoles; and the cyanophilic cells, in which the protoplasm colors 
dark blue with hematoxylin, and rarely contains vacuoles. The protoplasm of the 
chromophobic cells does not stain. Some authors consider that these distinctions 
are not morphologic, but only indicate that the different cells are in different stages 
of secretory activity. The posterior part (pars intermedia) of the anterior lobe 
usually contains, in man, a small bilobed cavity lined with cylindrical ciliated 
epithelium. In addition, there are also a few larger cavities lined by columnar or 
polygonal epithelium, and usually filled with colloid material. The posterior or 
nervous lobe consists of neuroglia tissue, and, according to Berkeley, a few ganglion- 
cells containing an excess of pigment, and some varicose fibers may be found in it. 
Kolliker, however, denies that there is any nervous tissue at all in the posterior lobe, 
and has been able to find nothing but neuroglia. It contains epithelial cells derived 
from the pars intermedia and a certain amount of colloid matter. 

If we can believe the assertions of those who have systematically 
examined large numbers of these bodies, a normal gland is the exception; 
thus, Schonemann found only 27 normal specimens in 110 cases, and 
Comte 33 in 108. 

Hypertrophy of the hypophysis occurs in cretinism, myxedema, 
and acromegaly. In some of these cases the enlargement is due to 
tumor formation; in others, particularly in those occurring as a result 
of removal of the thyroid gland, it appears to be compensatory, or 
rather, as the functions of this gland and the thyroid cannot be exactly 
identical, at least vicarious. This enlargement, often apart from 
tumor formation, may be very considerable. De Conlon records a case 
in which the hypophysis weighed 1.55 gm., and, aside from an apparent 
proliferation of the epithelium cells, was normal in structure. 

Circulatory Disturbances. — The gland is excessively vascular. It 
is possible that in some cases this vascularity may increase and give 
rise to a true hyperemia, although it is difficult to be certain of this. 
Changes such as are found in the thyroid gland in exophthalmic goiter 
have certainly not been described. In case of passive congestion 
resulting from thrombosis of the cavernous sinuses edema may be 
present. Hemorrhage in the gland is a frequent agonal phenomenon. 
In these cases the blood-cells, normal in appearance, are found infiltra- 
ting the connective-tissue stroma. Hemorrhages during life may occa- 
sionally occur, and give rise to small, deeply pigmented areas of soften- 
ing, which ultimately form scars. 

Inflammation is usually secondary and suppurative. One of us 
has observed a case in which the anterior lobe was infected from the 
parotid gland, probably as a result of ascending infection along the retro- 
pharyngeal lymphatics. In this case the capsule enclosing the gland 
was inflamed, and there were small collections of round cells in the sub- 
stance. 



714 



A TEXT-BOOK OF PATHOLOGY 



Degenerations. — The most important and frequent is colloid degen- 
eration, the colloid material being found in the cavities of the epithelial 
nests, or even as small masses in the connective-tissue septa. This 
may be looked upon as almost physiologic. It seems to be increased 
in those conditions in which we have reason to suspect increased func- 
tional activity of the glands, but also is more pronounced in cases 
of partial atrophy. Amyloid infiltration occurring in the blood-vessels 
has been observed in cases of general amyloid disease. The walls of 
the blood-vessels frequently undergo hyaline degeneration in old age. 

A sort of cheesy or liquefactive necrosis is also observed in the 
center of adenomatous formations, and is probably, due to pressure- 
necrosis, as a result of the limited space in which the hypophysis is 
placed. 

Infectious Diseases. — Of the infectious inflammations, the only 
ones of importance are tuberculosis, in the form of miliary tubercles, and 
syphilis, in the form of gummatous nodules. Occasionally a large 
single gumma has been observed. 

Tumors are the most interesting and important pathological con- 
ditions that occur, and there is still considerable difference of opinion 
regarding their nature. 

Cysts are very common, particularly a form of cystic degeneration 
with distention of the follicles by colloid substance. These are almost 
normal in old age, the only interesting feature being the atrophy and 
disappearance of the epithelial cells. Teratoid cysts have been described, 
but are much less frequent than would be expected from the com- 
plicated embryology of the gland. Of this nature is the myoneuroma 
described by White. 

Of the pathologically malignant tumors, the most important is the 
sarcoma. This is usually round-cell or spindle-cell in type, and appar- 
ently springs from the capsule of the gland and replaces its substance, 
but rarely infiltrates the surrounding tissues or gives rise to metastasis. 
Cases have been reported as lymphosarcoma in which there were numer- 
ous collections of round cells in the alveoli of the connective tissue and 
some hypertrophy of the latter; apparently, however, no other lymphatic 
organs were involved. 

Glioma and endothelioma have been seen. 

Adenoma of the hypophysis causes increase in the size; the organ 
remains soft or may be slightly indurated, and is of normal color. The 
resistance of the bony structures that surround it may cause the gland 
to assume extraordinary shapes. Microscopically, there is proliferation 
of the epithelial cells, which form long tortuous and sometimes branched 
tubes, and often complete atrophy of the nervous lobe. These tumors 
have been described particularly in connection with the disease known 
as acromegaly. 

Pathological Physiology. — Removal of the posterior lobe of the 
pituitary body (Paulesco) seems to show that it is not essential to life. 
Removal of the anterior lobe is rapidly fatal, but partial ablation is 
followed by decreased growth, persistence of infantile characters, fat- 



DISEASES OF THE DUCTLESS GLANDS 



715 



ness, atrophy of the sexual glands, and enlargement of the thyroid. 
Feeding experiments and the use of extracts show that the posterior 
lobe elaborates a substance similar in action to epinephrin.. It raises 
blood-pressure and stimulates smooth muscle-fibres (intestine, uterus); 
is diuretic and galactagogue. It also affects carbohydrate metabolism, 
causing glycosuria when injected experimentally. 

The relation of the pituitary to acromegaly first opened the way to 
a recognition of the functions of the gland. In the majority of cases of 
acromegaly, adenoma of the pituitary occurs, and investigators agree that 
the cases where manifest disease of the pituitary is not found, func- 
tional hyperactivity is present. Secondary involvement of the poste- 
rior lobe (hypophysis) may occasion glycosuria, and the thyroid and 
sex glands may also be secondarily involved. 

Several types of hypophyseal disease are recognized, and it is at 
present difficult to determine the seat and nature of the disturbance 
of function. 

Gigantism has been found associated with disease of the anterior 
lobe when this occurs in early life, as acromegaly develops when the 
disease occurs in later years. Both conditions are ascribed to increased 
function of the anterior lobe. 

Infantilism, fatness, and lack of sexual development (Frohlich's 
syndrome) are ascribed to decreased function of the anterior lobe. 

Hyperglycemia and decreased carbohydrate tolerance are associated 
with primary or secondary involvement of the posterior lobe. 

Polyuria (diabetes insipidus) occurs in connection with diseases of 
the pituitary and adjacent structures. 

THE PINEAL GLAND, OR EPIPHYSIS CEREBRI 

The pineal gland, or epiphysis cerebri, is an outgrowth from the roof 
of the posterior portion of the anterior vesicle of the brain. Its base 
is soon constricted, and it is finally completely separated from the 
primary cerebral vesicle and enclosed in a sheath of connective tissue 
which is surrounded by pia mater. Histologically, it is found to consist 
of septa of connective tissue, dividing it into numerous alveoli, in which 
are found epithelial cells, some of which are branched. It is very 
vascular, and contains a plexus of sympathetic nerve-fibers. 

It has lately been asserted that this gland has something to do 
with nutrition in the young, assisting and regulating metabolism and 
growth. It is thought by some to regulate sexual development. 

At all ages it contains small calcareous concretions (acervulus, 
brain-sand), which must, therefore, be looked upon as physiological. 
It is sometimes enlarged in acromegaly and cretinism; this may be 
a result of simple hyperplasia of the epithelial structures, giving 
rise to adenomatous or strumous formations, or due to neoplasms. As 
a result of its position it may in these conditions occlude the aqueduct 
of Sylvius or the veins of Galen and produce hydrocephalus. Path- 
ologically, aside from the calcareous infiltration already mentioned, 



716 



A TEXT-BOOK OF PATHOLOGY 



hyaline degeneration of the blood-vessels may occur. There are usually 
signs of inflammation, more or less marked, in cases of meningitis, 
which may even lead to pus formation. Of the tumors, the most im- 
portant are probably sarcomata springing from the connective-tissue 
septa. Adenomata may also occur. Cystic conditions, associated with 
the presence of hair, cartilage, and other tissues, have been described. 

Tumors and other diseases of the epiphysis, aside from local effects, 
have been found to occasion premature growth and sexual development. 



CHAPTER VII 



DISEASES OF THE URINARY ORGANS 
The Kidneys 
congenital anomalies 

Absence of one of the kidneys is frequently observed. Occa- 
sionally one kidney, instead of being completely absent, is atrophic or 
hypoplastic, while the opposite kidney may undergo compensatory 
hypertrophy. Both kidneys may be wanting in certain monstrosities. 

Congenital lobulation is quite common and is usually bilateral. 
The kidney is divided into separate lobes by furrows of variable depth. 
Occasionally there is almost complete separation into numerous lobules. 

A few instances have been observed in which there was a third 
kidney, and usually in these cases two of the kidneys lying to one side 
of the spinal column were agglutinated. 

Fusion of the two kidneys may occur, and there may result a single 
large organ, with a double pelvis and ureter lying to one or the other 
side, or a horseshoe-kidney may be formed. In the latter the two organs, 
which are generally displaced far downward, are united at their lower 
ends by a commissure passing across the spine just above the lumbo- 
sacral junction. The commissure may consist of normal kidney tissue 
or may be fibrous, more commonly the former. 

Congenital cysts and other congenital diseases will be referred to 
below. 

CHANGES OF POSITION 

Congenital Malposition. — Not rarely one of the kidneys is displaced 
downward. It may even occupy the pelvis. In other cases it is dis- 
placed laterally or forward, and has been found immediately beneath the 
anterior abdominal walls. 

Acquired malpositions may result from pressure upon the organ, 
or from elongation of the peritoneal reflections covering the kidney 
and absorption of the perirenal fat. The right kidney is more fre- 
quently displaced than the left, and the condition is especially common 
in women. Repeated pregnancies, the effects of tight lacing, and dis- 
eases or displacement of the liver are prominent causes. Movability or 
displacement of the kidney may be but a part of a general visceral 
descent (splanchnoptosis) . 

Several grades of movability or displacement may be distinguished. 
In the first, the perirenal fat is wanting, and the kindey is more movable 
beneath its peritoneal covering than is normal. This occurs in a large 

717 



718 



A TEXT-BOOK OF PATHOLOGY 



proportion of women, and usually affects the right kidney. In more 
advanced grades the peritoneal reflection covering the kidney is elon- 
gated and considerable movability of the organ within the abdomen 
results. The kidney may be moved from side to side, downward as far 
as the pelvis in some cases, or upward to the normal position or under 
the ribs. In a third group of cases the kidney, lying within an elongated 
peritoneal pouch, is retained in an abnormal position by adhesions. 

Results. — Twisting of the pedicle may lead to serious circulatory 
disturbances, or twisting of the ureter with retention of urine, sometimes 
causing hydronephrosis. Pressure of the displaced right kidney upon 
the duodenum may lead to dilatation of the stomach. 

CIRCULATORY DISTURBANCES 

Anemia of the kidney may occur as a part of general anemia. The 
kidney is light in color and rather hard in the earlier stages; but if the 
anemia persists, degenerative softening and enlargement may ensue. 

Complete arrest of the blood-supply, produced experimentally, 
leads to rapid necrosis of the kidney, the organ becoming ashen-gray 
in color and of a homogeneous structure, so that the separate parts 
(cortex, medulla, pyramids) are indistinguishable. Near the cortex, 
where some circulation is maintained by the capsular vessels, fatty de- 
generation is observed. Somewhat similar changes are met with in cir- 
cumscribed areas in diseases in which the circulation in branches of the 
renal artery is obstructed. (See Embolism.) 

Active hyperemia of the kidney is generally a part of acute inflam- 
mation. It may result from irritant chemical poisons or from the toxic 
action of infectious poisons. The kidney is enlarged, dark red in color, 
and on section the cortical substance is found to be swollen and marked 
by dark red points — the Malpighian bodies. Sometimes punctate or 
linear hemorrhages may be observed. The urine is somewhat albumin- 
ous and hyaline casts occur. It is difficult to draw a sharp line between 
this condition and acute nephritis. 

Passive hyperemia occurs in cardiac and pulmonary diseases which 
impede the circulation, or rarely as a consequence of thrombosis of the 
inferior vena cava or renal veins, or of other local causes obstructing 
the circulation in the renal veins. The kidney is enlarged and, on section, 
the cortex is found to be swollen, the substance of the kidney dark red 
in color, particularly in the pyramids in the vicinity of the large veins. 
The Malpighian bodies may be distinctly enlarged and dark red. 

Long-standing passive congestion leads to reactive hyperplasia of 
the interstitial connective tissue of the organ, and thus to a form of 
secondary interstitial nephritis. In these cases the kidney becomes 
contracted, the surface somewhat irregular, and the capsule ofttimes 
adherent. The organ may be intensely hard and pigmented, and the 
term cyanotic induration is appropriate. 

The microscopical findings include enlargement of the tufts, with 
loss of the epithelium and distention of the capsule with albuminous 



DISEASES OF THE URINARY ORGANS 



719 



transudate, and hyaline or connective-tissue thickening of Bowman's 
capsule. There are various degenerations of the parenchyma, in re- 
sponse to which some of the epithelium shows multiplied nuclei or en- 
largement of the cell to appear like syncytial cells. There may be edema, 
small hemorrhages, and almost always an excess of deposited blood- 
pigment. Hyaline casts are always found. The connective tissue is 
irregularly increased over the organ. 

The urine in passive hyperemia is, as a rule, deficient in quantity, 
and contains variable quantities of albumin and hyaline or granular 
tube casts. 

Hemorrhage. — Punctate hemorrhages may occur in cases of intense 
active or passive hyperemia, the extravasation of blood occurring in the 
interstitial tissues, in the uriniferous 
tubules, or within the capsule of Bow- 
man. Similar hemorrhages may be ob- 
served in acute or chronic nephritis. In 
these cases the extravasation of blood 
may occur by diapedesis or by actual 
rupture of the capillaries. Small hemor- 
rhages may occur in the perirenal tissues 
in certain of the hemorrhagic diseases. 
Large hemorrhages occur within the kid- 
ney substance only in cases of trauma- 
tism. 

Edema of the kidney results from 
obstruction of its venous circulation. 
The kidney becomes enlarged and soft, 
and the spaces between the convoluted 
tubules (the primary lymphatic spaces) 
are distinctly enlarged. There is asso- 
ciated congestion in these cases. Simple 
edema of the kidney may result from 
obstruction of the urinary outflow. 

Thrombosis of the renal veins or 
their branches is rare. It causes intense hyperemia, hemorrhages, and 
edema, and later necrosis and degenerations. 

Embolism is very common in the branches of the renal arteries, 
especially in cases of disease of the aortic valves or atheroma of the 
aorta, with fibrinous deposits upon the atheromatous areas. The 
blood-vessels of the kidney correspond closely to the conception of 
terminal arteries, and infarction is, therefore, the usual result. In most 
cases the infarcts are light-colored areas (anemic infarcts) having a 
wedge shape, the base of the wedge being directed toward the capsule 
of the organ. A zone of reactive hyperemia or hemorrhage usually 
separates the infarct from the surrounding structures (Fig. 330). Less 
frequently there are purely hemorrhagic infarcts, the entire area being 
dark red in color. Minute emboli may lead merely to punctate hemor- 
rhages within the kidney, or to ecchymotic extravasations on the surface. 




Fig. 330. — Anemic infarcts of the 
kidney surrounded by a zone of hem- 
orrhagic infiltration (Kaufmann). 



720 



A TEXT-BOOK OF PATHOLOGY 



The white or anemic infarcts undergo gradual necrosis and absorp- 
tion, with cicatrization or encapsulation, the contents in the latter 
case remaining as a dry detritus. The hemorrhagic infarcts more com- 
monly soften, and finally terminate in cicatrization or in the formation 
of small cysts. In cases of infective embolism the anemic or hemor- 
rhagic infarct may rapidly break down and form a metastatic abscess. 

INFLAMMATIONS 

Inflammation of the kidneys may affect the substance (nephritis), 
the mucous membrane of the pelvis (pyelitis), or the capsule and per- 
ipheral portions (perinephritis). 

NEPHRITIS 

Nephritis is the term given to a number of forms of degeneration 
and inflammation of the substance of the kidney. The term "Bright's 
disease" is a clinical rather than pathological one, being applied to 
various kinds of kidney disease attended with albuminuria and dropsy. 
As a rule, however, the name Bright's disease and nephritis are used 
synonymously. 

The classification of nephritis is quite difficult. Many complex 
classifications have been offered, but they are either inconsistent with 
clinical data or include too many subdivisions of main groups. There 
are three cardinal minute changes of nephritis — degeneration, exudation, 
and proliferation. These elements vary in intensity in different forms, 
but there seems no constant or absolute relationship between the varia- 
tions or combinations and clinical observations. We retain the old 
classification of nephritis because it furnishes the best basis for com- 
parison of clinical with pathological findings. All observers agree that 
clinical observations do not permit of accurate diagnosis of the patho- 
logical conditions in all cases, and attempts at elaborate subdivisions 
based upon the pathological histology are clinically useless. Under these 
circumstances the old and relatively crude classification here retained 
must still be regarded as the most satisfactory. 

Nephritis may be acute or chronic; and parenchymatous, diffuse, 
or interstitial. The term parenchymatous is applied to cases in which 
degenerative changes in the epithelium of the tubules or glomeruli are 
the most conspicuous feature ; the term diffuse is applied when exudative 
or proliferative changes affecting the connective tissues between the 
tubules and around the glomeruli and blood-vessels are associated in 
more or less equal proportions with the parenchymatous changes; and 
the term interstitial nephritis is used in cases in which exudative and 
especially proliferative changes are conspicuous. 

Etiology. — Nephritis is due in the majority of cases to irritants 
which reach the kidney through the circulation. Intense acute nephritis 
may result from various poisons, particularly such as attack the paren- 
chyma of organs, and are, therefore, known as parenchyma poisons. 
Among these, arsenic, mercury, phosphorus, cantharides, and turpen- 



DISEASES OF THE URINARY ORGANS 



721 



tine are conspicuous. A second group of cases, and perhaps the largest 
of all, owe their origin to infections of various kinds. Nephritis is a 
common complication or sequel of scarlet fever, cholera, septicemia, 
diphtheria, and many other infectious diseases. In these cases the 
micro-organisms themselves may reach the kidney through the circula- 
tion, as in typhoid fever, anthrax, or pneumonia, or the renal irritation 
may be caused by the toxins, as in cholera and diphtheria. Nephri- 
tis is common in streptococcus infections, but whether by circulating 
toxins or by the cocci themselves is not certain; the latter is probably 
more important. Certain chronic infections lead to nephritis by the 
action of the toxins or by slow nutritive disturbances. Such is the 
case in syphilis, tuberculosis, and malaria. Auto-intoxication occasions 
certain cases, as in the nephritis of gout and diabetes. 

In the minor infections, whether focal or generalized, low grades of 
degeneration or inflammation may be found in the kidney. These may 
be diffuse or insular, and may lead to chronic Bright's disease if the 
insults be repeated. Thus, in subinfection there may be a continued 
assault of very low power, but great in the aggregate. In focal infec- 
tion, again, from the tonsil or a joint for example, bacteria or their 
toxins may be carried by the blood to the kidney. Our newer concep- 
tions of these subdued forms of infection may thus explain some of the 
cases of nephritis heretofore called idiopathic or cryptogenic, the latter 
term being in a sense correct, as we seldom know the source and the 
infecting germ. 

In a small proportion of the cases nephritis results from irritants 
reaching the kidney through other channels than the circulation, as in 
pyelonephritis, a condition consequent upon inflammatory processes 
ascending from the bladder and ureters, or as in nephritis secondary to 
extrarenal disease (psoas abscess). 

Low-grade renal inflammation may result from chronic congestion 
of the kidneys in consequence of cardiac and pulmonary disease. In 
many cases arterial disease, whether or not affecting the renal arteries 
in common with other arteries of the body, may initiate renal changes 
eventuating in a chronic interstitial form of nephritis. 

Pathological Anatomy. — In considering the morbid anatomy the 
terms "parenchymatous" and "interstitial" are preserved, with the 
understanding that they are not strictly applicable to any given case. 
Purely parenchymatous inflammation does not exist, nor does intersti- 
tial nephritis occur without any parenchymatous change, but one or the 
other almost always predominates. Diffuse nephritis is considered 
under the heading Parenchymatous Nephritis. 

Parenchymatous degeneration and necrosis due to toxins or irritants 
of any kind may occasion disturbances of renal fanction entirely com- 
parable to that caused by more definitely inflammatory lesions. More- 
over, secondary changes in the connective tissues readily follow lesions 
of the parenchyma, as, on the other hand, interstitial processes are fol- 
lowed by parenchymatous degenerations. Thus it happens that purely 
parenchymatous or interstitial processes are exceptional. 

46 



722 



,,j A TEXT-BOOK OF PATHOLOGY 



Acute Parenchymatous Nephritis; Acute Bright's Disease 

This results most frequently from infectious fevers and toxic agents. 
It is more common in young persons than in the old. 

Acute Degenerative Nephritis. — The process in this condition 
may be almost purely parenchymatous in nature, and more nearly 
allied to pure degeneration than to inflammation. The epithelium of 
the tubules, especially in the convoluted portions, and to a certain extent 
also that covering the glomeruli, is swollen, cloudy, and considerably 
desquamated. Emigrated leukocytes, and occasionally red corpuscles, 
are found within the tubules and the capsule of the Malpighian bodies. 




Fig. 331. — Acute glomerulonephritis. 



The terms acute catarrhal or desquamative nephritis are more or less ap- 
propriate in such cases. The kidney is enlarged, somewhat swollen, and 
generally rather pale in color. The changes are most marked in the 
cortex, which is thicker than normal, and by its light color contrasts 
strongly with the pyramids. The capsule strips easily. In most cases 
the affection is one of slight severity. 

Acute Glomerulonephritis. — In another group of cases, occurring 
most commonly in scarlet fever, the glomeruli are primarily attacked 
and most severely affected throughout the disease, but the general 
epithelial structures are also implicated. Such cases are designated 
glomerulonephritis (Fig. 331). The epithelium of Bowman's capsule may 



DISEASES OF THE URINARY ORGANS 



723 



or may not be involved; when it is, the cells are swollen and show 
hyaline change, and the capsular space contains an albuminous ex- 
udate. The Malpighian tuft is chiefly attacked; it is usually enlarged, 
and in the early stages shows an increase of cells, which may be so 
great as to completely obscure the capillaries. In the later stages the 
walls of the capillaries are thickened, the lobulation of the tuft is more 
distinct, and hyaline masses may be seen in some of the lobules. The 
ncrease of cells is chiefly due to proliferation of the vascular endo- 
thelium; however, polymorphonuclear leukocytes and lymphocytes 
may be present. Distinct hemorrhages into the capsular space and 
necrosis of the cells of the capsule and of the tuft sometimes occur. 

Acute diffuse nephritis is the ordinary form of acute Bright's dis- 
ease, and is the form in which either of the two preceding are prone 




Fig. 332. — Acute diffuse nephritis, in which the interstitial infiltration is marked. Note 
degeneration of epithelium, increase of nuclei, and the swelling of glomerulus and its cap- 
sular lining. 

to terminate. The kidney is enlarged, and sometimes congested and 
red in color; at other times it is light colored or even yellowish in con- 
sequence of the epithelial degeneration and the anemia caused by 
pressure due to the epithelial swelling. On section, the cortex is much 
increased in width, and when congestion exists it is more or less mottled, 
showing spots or streaks of reddish color, the intervening portions of 
the substance being grayish or yellowish in hue. In other cases the entire 
cortical substance is uniformly gray, or yellow. The latter appearance 



724 



A TEXT-BOOK OF PATHOLOGY 



is commonly found in cases of considerable duration. In intense acute 
cases there may be punctate or linear hemorrhages, especially toward 
the surface of the organ, and the entire organ may be of a dark red 
color. In all cases the capsule strips easily from the underlying sub- 
stance (Fig. 332). 

Microscopically, the changes are most varied. In all cases there 
is more or less degeneration of the epithelium of the convoluted tubules 
and of that in the Malpighian bodies. In the earlier stages the cells be- 
come swollen and granular (cloudy swelling), while in advanced stages 
they may be filled with granules or droplets of fat (fatty degeneration). 
On the other hand, cases of great intensity may be marked from the 
very first by complete necrosis of the epithelial cells. Similar changes 
may be met with in the epithelium of the Malpighian bodies, and the 
latter may be converted into granular masses in which the capillary 
tufts are more or less obscured. Associated with these purely parenchy- 
matous changes are found evidences of interstitial involvement in the 
presence of masses of round cells between the tubules and in the vicinity 
of the Malpighian bodies. Active proliferation of the connective tissues 
is also observed, though less markedly, in the same situations. Certain 
cases are distinguished by their special tendency to hemorrhagic ex- 
travasations into and around the tubules and into the Malpighian 
bodies. To such the name acute hemorrhagic nephritis is sometimes 
applied. This variety is especially common in intense septic or infec- 
tious cases, particularly such as are attended with minute embolism of 
the renal arterioles. 

Acute Interstitial Nephritis 

Nonsuppurative acute interstitial nephritis may occur during 
the course of an infectious disease. The kidney is of a grayish 
opaque color, usually mottled with irregular hyperemic areas. On 
section, the normal markings are somewhat obliterated, and the 
contrast between the cortex and the pyramids is less marked. The 
interstitial change may be diffuse or focalized. It is usually most 
marked at the juncture of the cortex and medulla, in the region of a 
glomerulus or directly under the capsule. The cells found in these 
areas are proliferating connective-tissue cells, polymorphonuclear leuko- 
cytes, lymphocytes, or plasma-cells. Degeneration of the epithelial cells 
in the neighboring tubules may or may not be present. The blood-ves- 
sels of the kidney are always involved. 

Suppurative nephritis may result from metastatic involvement of 
the kidneys in cases of general septicopyemia, from ascending inflam- 
mation in association with pyelitis, or from involvement of the kidney 
in cases of suppurative disease in the vicinity. 

Embolic suppurative nephritis is characterized by the formation of 
small foci of suppuration in the substance of the organ, especially toward 
the periphery. These may occur as mere points of yellowish color, or 
they may be surrounded by a considerable zone of hemorrhagic infil- 



DISEASES OF THE URINARY ORGANS 



725 



tration. The surface of the organ may be studded with small elevated 
points, and as the process advances larger foci may form by confluence. 
Microscopically, the changes are found especially in the vicinity of the 
Malpighian bodies. Small capillaries are commonly found more or less 
obstructed with embolic plugs. Hemorrhagic extravasation is usually 
marked, and the accumulation of leukocytes leading to suppuration 
is the characteristic feature. Degenerative changes are seen in the 
epithelium of the vicinity, and, if the case has persisted for a certain 
length of time, the parenchymatous changes may be quite exten- 
sive. 

In certain infectious fevers (pneumonia, typhoid fever, anthrax) 
micro-organisms escape from the blood through the kidneys. In such 
cases it is possible that the bacteria which have been excreted may 
cause infection in the lower parts of the uriniferous tubules. The 
occurrence of such nephritis is uncertain. 

Suppurative pyelonephritis occurs in cases of suppurative pyelitis, 
especially in consequence of impaction of calculi in the pelvis. It is occa- 
sioned in most instances by ascending 
infection due to extension by sur- 
face continuity from lesions in an ob- 
structed pelvis or ureter or along the 
lymphatics of their walls. When these 
passages are not obstructed the secon- 
dary lesions in all probability arise by 
hematogenic infection. When the 
inflammation has started in the blad- 
der wall bilateral lesions are common, 
while only one kidney is affected 
should the infection begin in the 
ureter above its insertion in the vesi- 

i n lines of ascending suppuration (Kauf- 

Cal wall. mann). 

In the earlier stages small linear 
areas of light color are seen in the pyramids and medulla, running 
radially from the apex, and, microscopically, these are found to be 
uriniferous tubules infiltrated with pus-cells (Fig. 333). In the later 
stages these may run together, forming purulent collections of consid- 
erable size. The outer portions of the medulla and the cortex are 
only secondarily involved, and the suppurative areas here assume a 
more rounded shape. Pyelonephritis may terminate by rupture of the 
abscesses into the pelvis of the kidney and the discharge of the pus with 
the urine; by rupture on the surface of the kidney, causing perinephric 
abscess; or by inspissation and calcareous infiltration of the contents of 
the abscess. When discharge has taken place, or when inspissation 
occurs, induration and cicatrization of the diseased areas result. A 
considerable portion of the kidney may be thus converted into scar 
tissue. 

Suppurative nephritis, following suppuration around the kidney, 

leads to the formation of superficial abscesses and erosions. 




Fig. 333. — Pyelonephritis, showing 



726 



A TEXT-BOOK OF PATHOLOGY 



CHRONIC NEPHRITIS 

Chronic nephritis presents itself in varieties allied to the acute 
forms, and we may distinguish chronic parenchymatous and chronic 
interstitial nephritis. The former is practically always a diffuse process, 
presenting no such limitations to the epithelium of the tubules or to the 
glomeruli as are witnessed in the acute disease. Chronic interstitial 
nephritis is characterized mainly by hyperplasia of the connective 
tissue. 

CHRONIC PARENCHYMATOUS NEPHRITIS 

Chronic parenchymatous nephritis in most cases results from 
acute attacks which have become chronic by continuation or repeti- 
tion. It occurs after various infectious diseases, in consequence of 
alcoholism, or in an obscure manner, auto-intoxication probably ac- 
counting for some of the last group of cases. 

Pathological Anatomy. — The kidney is usually enlarged, and on 
section the cortical substance is often increased in width. The color 
is most frequently grayish or yellowish in consequence of the disease 
of the epithelium and of the anemia caused by the swelling of the cells. 
The pyramids may be quite red and swollen, or may be compressed 
and light in color. The capsule strips easily, and the substance of the 
organ is only moderately firm; sometimes, indeed, it is quite soft. To 
this form of chronic parenchymatous nephritis the term large white 
kidney is often applied. In other cases the substance of the organ may 
be quite red in color, or may be mottled, light areas of yellowish or gray 
color alternating with congested portions. In such cases careful ex- 
amination may show punctate or linear extravasations of blood, and the 
term chronic hemorrhagic nephritis is not inappropriate. The kidney 
is enlarged, as in the first variety, the cortex thick, and the capsule 
easily removed. In either case small cysts may form in the substance 
of the organ or upon the surface by distention of the convoluted tubules 
or capsules of Bowman (Fig. 334). 

In the later stages of chronic parenchymatous nephritis the de- 
generative processes in the epithelium become pronounced, and the 
organ may grow progressively lighter in color and more fatty in appear- 
ance, with streaks of fat running up between the stria? from the pelvis. 
Some investigators would view the pallor of the large white kidney as 
due to protagon in a finely granular state in the renal cells, and not to 
fat. At the same time interstitial processes associate themselves, and 
the substance of the organ becomes more firm and the kidney may be 
reduced in size. Attachments are formed between the substance and 
the capsule, which is no longer removable without laceration of the 
underlying substance. This terminal form of chronic parenchymatous 
nephritis has been designated as fatty contracting kidney, or as secondary 
interstitial nephritis, according to the amount of fatty parenchymatous 
change or of interstitial overgrowth present in the individual case 
(see p. 729). 



DISEASES OF THE URINARY ORGANS 727 

Microscopically, chronic parenchymatous nephritis is marked by 
striking degenerative changes in the epithelial cells of the convoluted 
tubules, and to a less extent in those lining the capsule of Bowman 
and covering the Malpighian tufts (Fig. 335). The epithelium of the 
tubules is at first swollen and finely granular (cloudy swelling), the 




Fig. 334. — Chronic parenchymatous nephritis with large and small retention cysts. 

nucleus being obscured and the cells oftentimes becoming fused. In 
moderately advanced cases it is rather characteristic to see a low even 
lining of fused epithelia, sometimes with a rather frayed edge toward the 
lumen (Fig. 336). In the more advanced stages of the process marked 
fatty degeneration of the cells is discovered, and they may break down 



728 



A TEXT-BOOK OF PATHOLOGY 



completely, so that the lumen of the tubule is filled with fatty and gran- 
ular detritus (Fig. 336). Extravasations of leukocytes or of red blood- 




Fig. 335. — Chronic parenchymatous nephritis, showing marked involvement of the Mal- 
pighian body and considerable interstitial change. 

corpuscles may take place, especially in the form known as hemorrhagic 
nephritis. Many of the tubules may be filled with tube-casts of hyaline 




Fig 336. — Chronic parenchymatous nephritis: a, a, a, Convoluted tubules with cloudy 
swelling of the epithelium; b, b, b, glomeruli, more or less degenerated; c, c, atrophic tu- 
bules; d, sclerotic interstitial tissue; e, round-cell infiltration; /, blood-vessel; g, g, g, g, g, 
g, tube-casts in tubules (Kaufmann). 



or, more frequently, of granular appearance. The Malpighian bodies 
are usually simultaneously, though perhaps less markedly, affected. 



DISEASES OF THE URINARY ORGANS 



729 



The epithelium in the latter is proliferated and degenerated, and the 
vascular tuft may present considerable hyaline degeneration. In the 
hemorrhagic variety the capsular space may be completely filled 
with extravasated blood. Side by side with these parenchymatous 
changes may be seen changes in the interstitial tissues. Notably, there 
are proliferation and thickening of the capsule of Bowman and of 
the connective tissues between the tubules. Sometimes cases are seen 
in which connective-tissue increase about the capsule of Bowman is 
prominent, but in this form of nephritis the fibrous tissue is more diffuse 
than in the primary chronic interstitial form. In advanced stages 
these interstitial changes are always present, and in those cases known 
as secondary interstitial nephritis the connective-tissue hyperplasia is 
the predominating condition. The walls of the small blood-vessels of 
the kidney are usually thickened by hyperplasia. 

CHRONIC INTERSTITIAL NEPHRITIS 

Chronic interstitial nephritis leads to the formation of a contracted 
kidney. This may be a secondary form of nephritis following passive 
congestion or chronic parenchymatous nephritis, or it may be primary, 
when it is often associated with diffuse arteriosclerosis. 




Fig. 337. — Chronic interstitial nephritis, showing small cystic dilatations of tubules. 

Secondary chronic interstitial nephritis is the terminal stage of 
certain cases of chronic parenchymatous nephritis, and results from a 
continuous hyperplasia of the interstitial tissues, with degeneration and 
atrophy of the parenchyma. The organ is reduced in size, and may be 



730 



A TEXT-BOOK OF PATHOLOGY 



quite irregular upon the surface, the irregularity taking the form of large 
depressions or of fine granulations. The capsule strips with difficulty, 
portions of the kidney substance remaining attached. On section, the 
kidney is found to be firmer than normal, and is of light color, often 
yellowish (fatty) in hue. The cortex may be nearly the normal thick- 
ness or may be considerably reduced. The small blood-vessels of the 
substance of the organ may be gaping and visibly sclerotic. 

Microscopically, the epithelium of the tubules is granular, fatty, or 
atrophic, and the cells are found detached in great numbers and occupy- 
ing the lumen of the tubules. The tubules themselves may be com- 
pressed by surrounding interstitial overgrowth, or may be distended 
even to the formation of cystic dilatations (Fig. 337). The capsule of 

Bowman is greatly thickened, and 
the Malpighian bodies may be much 
distorted and compressed. 

Primary Chronic Interstitial 
Nephritis; Red Granular Kid= 
ney; Arteriosclerotic Nephritis; 
Gouty Nephritis. — All of these 
terms have been applied to a form 
of interstitial nephritis probably 
produced by irritants conveyed 
through the circulation. As has 
been suggested on p. 721, in dis- 
cussing the etiology of nephritis, 
repeated insults to the parenchyma, 
or congestion and edema of the sup- 
porting tissue by circulating poisons 
is responded to by nature in the 
form of connective-tissue forma- 
tion. It occurs in consequence of 
^. „ , . . alcoholism,* syphilis, gout, chronic 

lig. 338. — Chrome interstitial nephritis: , 1 . , . , . „ 

granular kidney (Orth). plumbism, chronic cachexias 01 

other kinds, and various forms of 
subinfection, or as a part of the effects of focal infection. It is not 
rarely associated with diffuse arteriosclerosis. A certain amount of 
interstitial nephritis of this variety is a natural lesion of old age. 

Pathological Anatomy. — The kidney is usually decreased in size, 
and sometimes may be very much contracted. In other cases the reduc- 
tion in the dimensions is inconsiderable, and the size may even be in- 
creased. The surface is irregular, and, on removal of the capsule, is 
found to be finely granular or irregularly lobulated (Fig. 338). The 
capsule itself strips with difficulty. Small cysts may be seen upon the 
surface. On section, the substance is firm, and may sometimes be 
almost cartilaginous in consistence. The cortex is narrow, often being 
reduced to one-quarter or one-sixth its normal width, while the pyramids 
may be increased in size or contracted like the cortex, and not rarely 
show dense white sclerotic tissue radiating from the apices. In gouty 




DISEASES OF THE URINARY ORGANS 



731 



cases deposits of urates may be observed in the same situation. The 
color of the kidney varies, but is usually grayish brown or gray. The 
blood-vessels in the substance of the organ are usually gaping and their 
walls visibly thickened. 

Microscopically, chronic interstitial nephritis is characterized by 
great hyperplasia of the connective tissue surrounding the Malpighian 




Vi: 




Fig. 339. — Chronic interstitial nephritis: great increase of connective tissue around the 
glomeruli, renal tubules, and blood-vessels. 

bodies and the convoluted tubules, and by hyperplasia of the walls of 
the blood-vessels (Fig. 339). The overgrowth of connective tissue may 
be irregular in its distribution and may 
vary greatly in amount. In beginning 
cases there is only moderate thickening 
of the capsules of Bowman and of the 
intertubular tissues and walls of the 
blood-vessels. In ordinary cases fibrous 
thickening of the Malpighian capsules, 
with new formed connective tissue con- 
sisting of young connective-tissue cells 
and round infiltration cells between the 
tubules and sclerotic thickening of the 
blood-vessels, constitute the striking 
microscopical features (Fig. 340) . In the 
most pronounced cases the kidney sub- 
stance is almost wholly transformed into 
fibrous tissue of dense sclerotic char- 
acter. The epithelium undergoes progressive atrophy, the cells 
shrinking in size and becoming granular and loosened from the base- 
ment-membrane. Hyaline or granular tube-casts may be found within 




Fig. 340. — Chronic interstitial neph- 
ritis (from a photograph bv Dr. Wm. 
M. Gray). 



732 



A TEXT-BOOK OF PATHOLOGY 



the tubules, and the latter are compressed by contraction of the new 
formed connective tissue, the parts distal to the constriction being 
distended with secretion or seemingly dilated by the disappearance of 
the epithelium. 

The arteriosclerotic kidney, while in the main closely like the group 
description just given, presents a few features by which it can be recog- 
nized pathologically. It is a small, hard, granular, reddish or red-gray 
organ, usually without cysts; it has an adherent capsule, and upon 
section shows a narrowing of both cortex and medulla, prominent 
vessels with wide walls, and distinct glomeruli. Microscopically, the 
connective-tissue increase is greatest in the vicinity of vessels and in 
their walls, and it is only late that glomeruli and tubules are wholly 
obliterated. The tufts may show hyaline degeneration by reason of the 
interference with their blood-supply. Arteriosclerosis being an irregular 
process, it follows that not all sections of the kidney will be affected the 
same way; while in chronic nephritis of primary character or that suc- 
ceeding an acute diffuse affection pathological alterations are more 
evenly distributed through the organ. 

Pathological Physiology of Nephritis. — The effect of acute or 
chronic nephritis varies greatly in individual cases. Profound systemic 
disturbances in acute cases are doubtless often the result of the action 
of toxic substances which caused the nephritis, rather than of the dis- 
ease of the kidneys itself. In uncomplicated cases of acute or chronic 
nephritis the influence upon the general metabolism is seemingly slight. 
Investigations have not as yet shown any decided increase in the meta- 
bolic consumption of the tissues, and no specific disturbances of metabo- 
lism of any sort have been discovered. It is very likely, however, that 
extensive disease of the kidneys does exercise some influence, since 
these organs undoubtedly have actual glandular functions and are not 
merely passive agents for the filtration of the blood and the excretion of 
urine. The peculiar intoxication which occurs in nephritis, and to which 
the name uremia (q. v.) is applied, has received no satisfactory explana- 
tion. It is probable that substances normally excreted in the urine 
are retained in the blood and accumulate to such an extent that in- 
toxication results. It is also likely that substances which are normally 
elaborated by the kidneys and excreted in altered forms remain in the 
blood and occasion disturbances. Marked retention of non-protein 
nitrogen is found in nephritics and especially in uremia. During 
the progress of uremia there seems undoubtedly to be active tissue 
consumption, but accurate studies are wanting. Excretion of sodium 
chlorid is decidedly diminished in nephritics, and the retention of this 
salt is a factor in the development of the edema of renal disease. 

Gastro-intestinal symptoms are frequent in renal disease. In a 
notable proportion of cases the gastric secretion has been found defi- 
cient, and this may account for some of the disturbances. Putrefactive 
processes in the intestines have also been demonstrated in some cases, 
being evidenced by the increased quantity Of ethereal sulphates in the 
urine. In the later stages of nephritis, and especially in uremia, severe gas- 



DISEASES OP THE URINARY ORGANS 



733 



tro-intestinal disorders sometimes develop. These have been explained 
by the assumption that urea is excreted through the gastro-intestinal 
mucous membrane, and undergoes ammoniacal decomposition within 
the digestive tract. The ammonia formed by this decomposition is 
supposed to be the immediate cause of the gastro-intestinal disturbance. 

The urine in nephritis is of the greatest interest. In acute cases, 
and sometimes in chronic forms, it suffers notable change of appear- 
ance by admixture of blood. In other instances the color and 
physical properties are to a large extent dependent upon the amount 
of urine excreted. As a rule, the quantity of urine is decreased in 
nephritis. The nitrogenous elimination is of particular interest. In 
acute cases, in which the quantity of urine is greatly deficient, there 
is undoubtedly an insufficient excretion of nitrogen in the urine; 
subsequently the nitrogenous element may be excreted in increased 
quantities. In acute nephritis without marked diminution in the 
quantity of urine the nitrogenous elimination may remain satisfac- 
tory. In chronic nephritis the elimination of nitrogen in the urine 
may be reduced, both in the parenchymatous and interstitial forms of 
the disease. Nitrogen retention is not invariable, and from time to 
time periods of increased elimination may occur. The amount of urea 
is very commonly decreased; in part this may be compensated for by 
increased elimination through the skin and intestines. The uric acid is 
usually decreased in quantity, but may be entirely normal in any form 
of nephritis, and may in some instances be temporarily increased. 
Ammonia is present in normal quantities; during uremia it may be 
increased. Xanthin may be present in increased quantities, and crea- 
tinin is reduced in quantity. 

The urine in nephritis presents two striking peculiarities: the pres- 
ence of albumin, discoverable by chemical examination, and the pres- 
ence of tube-casts. Albuminuria is an almost constant symptom, though 
occasionally, in chronic interstitial nephritis, the amount may be so 
small that it is not detected by the cruder tests. The more delicate 
methods will probably detect albumin in every case. Serum-albumin 
is the more important form, but globulin occurs in small amounts in 
every case when albumin is excreted. In hemorrhagic forms of acute 
or chronic nephritis and in cases complicated by amyloid degeneration, 
globulin may be found in considerable quantity. 

Albumin is excreted by both the glomeruli and the tubules, but the 
former is by far the more important. Damaged epithelium will permit 
albumin to pass; it is not necessary that the cells be desquamated. 

The tube-casts met with in nephritis are casts formed within the 
convoluted tubules, or more rarely in other parts, and are composed 
of albuminoid substances and possibly sometimes of fibrin. They are 
formed partly of materials which have accumulated in the tubules by 
exudation, partly of the granular detritus of the degenerated epithelium, 
or of red and white blood-corpuscles. We may distinguish a number of 
varieties, viz., hyaline, cellular, crystalline, and granular casts and 
cylindroids. 



734 



A TEXT-BOOK OF PATHOLOGY 



Hyaline casts are clear, rounded bodies having a diameter of from 
0.01 to 0.03 mm. and a variable length. Sometimes they are quite 
short; at other times they extend across several fields of the microscope. 
They may be straight, or spiral or contorted. Sometimes they are so 
transparent and light colored that they are scarcely visible, or, on the 
other hand,- they may be of a denser structure and less transparent. 
Hyaline casts are frequently met with in simple congestion of the kidney 
and in icterus unassociated with discoverable nephritis. They are most 
abundant in acute parenchymatous nephritis, but are met with also in 
chronic parenchymatous and interstitial nephritis. A form of hyaline 
cast known as the waxy cast is met with, sometimes in acute, but more 
commonly in chronic, nephritis (Fig. 341). It is distinguished by the 
moulded, wax-like appearance and by its apparent rigidity. 

Cellular Casts. — The most frequent form is that in which the sur- 
face of a hyaline or granular cast is covered with epithelial cells that 




Fig. 341. — Waxy hyaline casts. Fig. 342. — Blood-casts, composed wholly 

of red or white corpuscles, or hyaline sub- 
stance covered with blood-corpuscles. 



have detached themselves from the tubules. The entire surface may be 
covered, or there may be but a few cells here and there. This form is 
found especially in acute parenchymatous nephritis. Leukocytic casts 
are moulds of the tubules composed of masses of leukocytes. They are 
found especially in purulent pyelonephritis. Occasionally leukocytes 
are found upon the surface of other casts. Blood-casts, composed of 
red blood-corpuscles or of blood-pigment formed by disintegrated red 
corpuscles, are frequently observed in acute and chronic hemorrhagic 
nephritis (Fig. 342). 

Crystalline Casts. — Moulds of the tubules, composed of uric acid 
or oxalate of lime, are sometimes observed in chronic nephritis, when 
there is a tendency to the deposition of the crystals named (Fig. 343, A). 
Similar formations may be met with in the urine of the newborn inde- 
pendently of nephritis (see page 740). 



DISEASES OF THE URINARY ORGANS 



735 



Granular casts may be light or dark, according to the amount and 
character of the granular material. They are composed of substances 
derived from broken-down epithelial cells, and are especially common 
in chronic nephritis, though they may occur in quite acute cases. Some- 
times, instead of granular matter, the debris of the epithelial cells 
occurs as oil drops, and the term fatty casts is appropriately applied 





Fig. 343. — A, Tube-casts, composed of uric-acid crystals. B, Granular and fatty casts 
and two compound granular cells. 



(Fig. 343, B). The diameter and length of granular casts vary con- 
siderably. As a rule, the diameter is about the same as that of the 
hyaline casts, but the length is rarely as great. 

Cylindroids are formations resembling casts more or less closely, 
Sometimes they appear as thread-like formations, rounded or flat, 
and occurring singly or in twisted bunches. 
In other cases they may be quite similar to 
hyaline casts, though distinguished by a long, 
tapering end or tail (Fig. 344). Cylindroids 
occur in conditions of renal irritation not 
sufficient to constitute nephritis, as well as 
in cases of genuine nephritis. They are also 
supposed to be produced in the tubular glands 
of other parts of the genito-urinary tract, as in 
the glands of Cowper. 

Other Constituents of the Urine. — Various 
cellular constituents are found in nephritis. 
In acute and in chronic hemorrhagic neph- 
ritis white and red blood-corpuscles are fre- 
quently observed; and epithelial cells are 
more or less abundant in all forms of paren- 
chymatous nephritis. In the acute varieties swollen and granular 
rounded cells are observed; in the more chronic forms, particularly 
when fatty degeneration is pronounced, epithelial cells or leukocytes 
densely filled with dark granular or globular fat are conspicuous. The 
term compound granule cell has been applied to these cells. 




Fig. 344. — Cylindroids: a 
and b, Cast-like forms ; c, fila- 
mentous forms. 



736 



A TEXT-BOOK OF PATHOLOGY 



Results of Nephritis. — Nephritis leads to notable changes in the 
entire organism, and particularly in the vascular system. 

Cardiac Changes. — In acute nephritis there may be associated acute 
degenerative or inflammatory lesions of the heart muscle, and cardiac 
dilatation may occur. These, however, are usually results of the infec- 
tious or toxic cause underlying the nephritis, rather than results of the 
nephritis itself. When parenchymatous nephritis becomes subacute 
or chronic, hypertrophy of the heart (notably of the left ventricle) takes 
place, and this may reach extreme proportions in chronic interstitial 
nephritis. The cause of the hypertrophy of the heart has occasioned 
much controversy. It seems likely that it is in large part the result of 
irritation and overstimulation of the heart muscle by substances re- 
tained in the blood, instead of being excreted. These retained sub- 
stances seem to have the effect of raising the vascular pressure, a factor 
of undoubted importance in throwing extra work on the heart. The 
obstruction to the circulation occasioned by thickening of the walls of 
the renal vessels is of little moment; and the theory that the cardiac 
hypertrophy is due to a hydremic condition and increased quantity of 
blood, in consequence of retention of water in the system, is negatived 
by the fact that such hydremic excess of blood is certainly absent in 
many cases. Associated arteriosclerosis is undoubtedly one of the im- 
portant factors in the production of cardiac hypertrophy. 

Arteriosclerosis. — The arteries are frequently sclerotic in cases 
of chronic nephritis. In part this is due to the direct action of toxic 
products of improper metabolism occurring in Bright's disease; in part 
it is a coincidental or an antecedent condition. 

Acute inflammatory lesions of the serous membranes, and to a less 
extent of the mucous membranes, sometimes occur in Bright's disease. 
Acute endocarditis, acute pericarditis, and pleurisy are the most fre- 
quent conditions. Of the inflammatory conditions of the mucous mem- 
branes, tonsillitis and pharyngitis are not infrequent. Enteritis, even 
of ulcerative type, may occur, especially in chronic nephritis. This, in 
part, seems to result from vicarious excretion of irritant matters from 
the intestinal mucosa. 

Edema, or dropsy, is a frequent manifestation of nephritis. It is 
most frequent in the parenchymatous forms, particularly in such as 
occasion changes in the glomeruli and other vascular portions of the 
kidney. In chronic interstitial nephritis dropsy is rarely observed 
until the late stages, when manifest arterial disease and failing circula- 
tion from cardiac weakness have supervened. The edema usually 
begins in the loose subcutaneous tissues of the eyelids and hands, but 
extends to all parts of the body, causing anasarca. Internal edema, and 
especially edema of the lungs, may be met with. 

Uremia is the name applied to certain clinical manifestations prob- 
ably caused by the retention of toxic substances in the blood which 
ordinarily are excreted with the urine. The nature of the substance or 
substances in question remains obscure. Neither urea, potassium or 
ammonium salts, uric acid, nor various other constituents of the urine 



DISEASES OF THE URINARY ORGANS 



737 



alone produce uremic manifestations, though the injection into animals 
of some of these may cause toxic symptoms, such as convulsions or 
coma. It may be that uremia is caused by the conjoined action of a 
number of such toxic bodies, but it is not improbable that the poisons 
are substances as yet undiscovered. The theory that uremia is due to 
edema or anemia of the brain may be definitely abandoned. The view 
has been expresssed that toxic substances are liberated by the renal 
cells as a consequence of their degeneration, and that these "nephrotox- 
ins" are concerned in uremia. This theory is still entirely speculative. 

ATROPHY AND HYPERTROPHY 

Atrophy of the kidney may be congenital (hypoplasia), or may 
occur in old age (senile atrophy). In the latter case (sometimes called 
"senile nephritis") the kidney is small, hard, and usually darker in color 
than normal. The irregular atrophy of the parenchyma leads to irregu- 
larities upon the surface of the organ. The capsule may be thickened, 
and not rarely the perirenal fat is abundant, and considerable fatty 
deposit occurs beneath the mucous membrane of the pelvis. 

Microscopically, the renal cells are small in size, somewhat dark 
and granular. They may disappear entirely from the tubules in places, 
and the intertubular tissue and the basement-membrane are corre- 
spondingly thickened. The Malpighian bodies may be converted into 
contracted fibrous areas. In some cases the interstitial processes become 
so pronounced that the kidney presents the picture of interstitial nephri- 
tis. These cases are particularly met with in persons of advanced years 
having arteriosclerosis. (See Chronic Interstitial Nephritis.) 

Hypertrophy may affect one kidney when its fellow is congenitally 
wanting, has become diseased, or has been removed. Under these cir- 
cumstances the remaining or healthy organ sometimes undergoes con- 
siderable hypertrophy. The appearance is that of a much enlarged 
but otherwise normal kidney. 

Microscopically, there may be simply increase of the size of the 
tubules, or in cases in which the compensatory hypertrophy has begun 
before the completion of development there may be actual increase in 
the number of tubules and Malpighian bodies. 

DEGENERATIONS 

Parenchymatous degeneration, or cloudy swelling, occurs in the 
kidneys in consequence of the action of various poisons, infectious or 
chemical. It is met with in practically all cases of diphtheria, scarlet 
fever, and cholera, and less commonly in many other infectious dis- 
eases. Among the poisons the various parenchyma poisons (q. v., Part I) 
are all capable of attacking the kidney and producing cloudy swelling. 
In case of either toxic or infectious degenerations, however, the process 
is prone to become more serious and to terminate in acute parenchy- 
matous nephritis. No sharp dividing-line can be drawn between the 
two conditions. 

47 



738 



A TEXT-BOOK OF PATHOLOGY 



The kidney is somewhat increased in size, is softer than normal, 
and, on section, the cortex is yellowish or of light grayish color (Fig. 345). 
The Malpighian bodies may be prominent as red spots lying in the light- 
colored renal tissue. The pyramids are often congested and contrast 
strongly with the cortical substance. 

Microscopically, fine granulation of the cells of the convoluted 
or other tubules is the striking feature. The nuclei of the cells are ob- 
scured, and at times all of the cells of the tubules apparently become 
fused. Exudative changes and hyperplasia of the interstitial tissues 
are wanting in a purely degenerative condition. Frequently the kidney 
is restored to the normal condition, but, on the other hand, acute 
Bright's disease or fatty degeneration may ensue. 

Fatty Degeneration. — This occurs in consequence of the last- 
described condition, or independently in consequence of general anemia 




Fig. 345. — Parenchymatous degeneration of the kidney, from a case of cholera (modified 

from Kast and Rumpel). 

and systemic disorders, as in progressive pernicious anemia and tuber- 
culosis. Fatty degeneration of the kidney frequently occurs in the 
course of pregnancy, when it is due to disturbance of the circulation 
in the kidneys or possibly to obstruction of the ureters. In these cases 
the process usually advances to the condition of diffuse nephritis. 

In pure fatty degeneration the kidney is about the normal size, 
or often smaller than normal; is soft; and, on section, the cortex has 
about the normal width. The color is uniformly yellowish or mottled, 
certain areas being yellowish in color and others normal or perhaps 
hyperemie. Usually the surface of the kidney is smooth, but some- 
times localized spots of degeneration may become depressed and give 
rise to irregularities. 

Microscopically, the epithelial cells are granular or filled with oil- 
drops (Fig. 346). Not rarely the cells are loosened and lie free within 
the lumen of the tubules. The basement-membrane and interstitial 
tissues may be somewhat thickened, either apparently or actually. 

Fatty infiltration is an unimportant condition. In the atrophic kid- 
neys of old age and in the contracted kidneys of chronic nephritis fatty 
infiltration of the areolar tissue beneath the mucosa of the pelvis is 



DISEASES OF THE URINARY ORGANS 



739 



frequently observed. Fatty infiltration of the epithelial cells may 
occur under normal conditions, or in cases in which the blood is sur- 
charged with fat (lipemia) and in which the kidneys are actively en- 
gaged in its excretion. Fatty infiltration of the perirenal cellular 
tissues occurs in general obesity, and sometimes as a localized affection 
in cases of advanced renal disease, particularly atrophy. 

Calcification may occur in diseased areas of the kidneys, as in 
degenerated and fibrosed areas, in old infarcts, and the like. Occa- 
sionally calcification occurs in the epithelial cells themselves, particu- 
larly in such as have undergone necrosis. This is particularly marked 
in certain poisonings (e. g., mercuric-chlorid-poisoning). Calcium salts 
are sometimes deposited in infarct arrangement in certain diseases of 
the skeleton, notably osteomalacia. This is a part of the so-called 
calcium metastasis. 



/ . • • ••• .•• • 



mi 



Fig. 346. — Fatty degeneration of the epithelium of the tubules, stained with osmic acid 

(Simmonds). 

Calcareous bodies in the cortex of the kidney are not infrequent. They 
are due to calcification of little cysts springing from the uriniferous 
tubules or Malpighian bodies. 

Glycogenic infiltration of the kidneys occurs in diabetes. It affects 
the epithelial cells, particularly those in the portions of the organ lying 
between the medulla and the cortex. The kidney is usually increased 
in size, the cortex broader than normal, and the consistency increased. 
The substance may be lighter colored and of homogeneous appearance. 
Microscopically, the epithelial cells, particularly those of the tubes of 
Henle, are found to be altered in character, the normal granular condi- 
tion of the protoplasm having disappeared. The glycogenic nature of 
the infiltrating substances is recognized by the dark-brown color ob- 
tained by staining fresh sections with iodin. 

Amyloid infiltration occurs in the kidneys under the same condi- 
tions as in the liver and spleen. It is most frequent in cases of chronic 
tuberculosis of the lungs, and occurs in cases of long-standing suppura- 



740 



A TEXT-BOOK OF PATHOLOGY 



tion connected with bone, in syphilis, and as a result of other cachexias. 
The kidney is enlarged, sometimes to twice its normal bulk, is harder 
than normal, and, on section, the substance is found light grayish in 
color. It may be uniformly grayish or waxy; or, on the other hand, 
it may be mottled, grayish areas alternating with portions of yellow 
color, the latter being due to fatty degeneration. Amyloid deposit be- 
gins in the small blood-vessels, particularly those of the Malpighian 
tufts, and spreads to the connective tissues of the organ, but does not 
involve the epithelium. 

Microscopically, the glomeruli may present spots of hyaline or homo- 
geneous appearance in which the capillaries seem completely disorgan- 
ized, and the entire glomerulus may be transformed into a transparent 
or translucent mass (Plate 13). The capsule is thickened and ofttimes 
simultaneously diseased. The tubules habitually contain hyaline casts. 
The organ becomes more or less anemic from obstruction of the capil- 
laries, and sooner or later fatty degeneration of the epithelial cells takes 
place. Inflammatory processes are usually wanting, but nephritis may 
become associated with amyloid degeneration, and the latter process may 
occur in kidneys primarily the seat of nephritis. Litten finds that the 
glomeruli are not always the first part affected ; neither is the muscularis 
of blood-vessels always the starting-point. The adventitia or intima may 
be first affected. He distinguishes the following varieties of amyloid 
kidney: (a) Pure amyloid kidney with amyloid change of the blood- 
vessels and with or without fatty change in the epithelium. Macro- 
scopically, the kidney may seem to be normal, but the iodin reaction 
indicates its true condition, (b) Large white amyloid kidney. This is 
the commonest form, and consists of amyloid degeneration plus chronic 
parenchymatous nephritis, (c) Amyloid contracted kidney is com- 
paratively rare, and a very rare form is (d), the association of acute neph- 
ritis with amyloid change in the blood-vessels. 

The urine in amyloid disease is albuminous and scanty; the pro- 
portion of serum-globulin is excessive. Not rarely it contains hyaline 
casts which respond more or less distinctly to the color-tests for amyloid 
substance, but these are not diagnostic, and it is doubtful whether they 
are, in reality, composed of amyloid material. 

CONCRETIONS IN THE URINIFEROUS TUBULES 

Various calcareous concretions, or "infarcts," occur in the uriniferous 
tubules, particularly in the large collecting tubules near their termina- 
tion at the apex of the pyramids. Collections of urates, particularly 
urate of ammonium, are frequently seen in the form of radiating lines of 
light grayish, yellowish, or reddish color, marking the pyramids near 
the apices in newborn infants. These consist of crystalline concretions 
filling the large uriniferous tubules, and have been considered as a valu- 
able medicolegal indication that the infant had breathed. They are not, 
however, sufficient proof. Sometimes the concretions are passed with 
the urine, and are discovered as large casts of conglomerated crystals. 
Less frequently other forms of crystals are met with in the infarcts of 



PLATE 13 




Amyloid infiltration of capillary walls in kidney glomerulus. 



DISEASES OF THE URINARY ORGANS 



741 



the newborn. Similar concretions occur in gouty individuals, particu- 
larly in aged persons, and calcium salts may be deposited when the 
blood is surcharged with them in consequence of diseases of the bones. 
Triple phosphates may be found as a consequence of obstruction of the 
urinary passages and stagnation of urine. 

Concretions composed of bilirubin may be formed in extreme jaun- 
dice, and particularly in the jaundice of the newborn. Infarcts com- 
posed of hemoglobin may be seen in cases of hemoglobinuria due to in- 
fectious and toxic causes. 

INFECTIOUS DISEASES 

Tuberculosis may occur in the kidney in the form of minute, grayish- 
white miliary tubercles as part of a general hematogenous tuberculosis. 
A second form, which is also hematogenic, is known as chronic local 
tuberculosis. In this form the substance of the kidney near the cortex, 
or sometimes that adjacent to the pelvis, is occupied by masses of cheesy 
tuberculous tissue, and there may be secondary miliary tuberculosis 
near by. Softening is prone to occur, and the tuberculous focus may dis- 
charge into the pelvis of the kidney, leaving a necrotic cavity. The 
entire organ may be honey-combed with cavities. Tuberculosis of the 
kidney may also result from ascending infection, being secondary to 
tuberculosis of the seminal vesicles, of the bladder, of the ureters, and of 
the pelvis of the kidney. The process first involves the discharging 
tubules at the apices of the pyramids and spreads outward toward the 
cortex. Cheesy foci are formed, which may soften and discharge into 
the pelvis, as in the case of chronic local tuberculosis of the kidney. It 
is difficult to determine whether tuberculosis of the kidneys is more fre- 
quently the result of urogenital tuberculosis primarily affecting the parts 
below, or the cause of the latter. Primary affection of the kidney is cer- 
tainly more common than many have been disposed to admit. 

Syphilis. — In the earlier stages of syphilis there may possibly be 
acute nephritis similar to that of other infectious diseases. Syphilis 
of long duration may lead to amyloid degeneration of the kidney or to 
chronic interstitial nephritis. Thickening of the blood-vessels is con- 
spicuous. In the latter case contractions of fibrous tissue leading to 
marked lobulation are rather characteristic. Syphilitic gummata are 
rare, but have been met with, and in their healing lead to marked scar 
formation. 

Lesions of leprosy, actinomycosis, and glanders have been observed. 

TUMORS 

Fibromata and lipomata may occasionally be met with in the 
kidney in the form of small rounded nodules. In association with 
calculous pyelitis and other conditions of the kidney leading to atrophy, 
the fatty tissue surrounding the kidney may be increased to such an 
extent as to constitute practically a fatty tumor. 

Leiomyoma is an occasional growth of the kidney. 



742 



A TEXT-BOOK OF PATHOLOGY 



The most important tumors of the kidney are classified nowadays 
under the teratomata; they are the hypernephroma or Grawitz tumor, 
and the adenosarcoma or Wilm's tumor. 

Hypernephroma. — Under the name of struma aberrata suprarena- 
le or hypernephroma, has been described a form of tumor of the kidney 




Fig. 347. — Hypernephroma of kidney, showing destruction of most of the kidney sub- 
stance. The tumor was yellow in color (from a specimen in the collection of Dr. Allen 
J. Smith). 




Fig. 348. — Finer structure of the adenomatous form of hypernephroma. 

which results (Grawitz) from splitting off of a remnant of the supra- 
renal capsule and its incorporation in the kidney, where it subsequently 
grows (Figs. 347, 348). Wilson would explain these tumors as remains 
of the primary kidney tubules, nephrogenic tissue in the Wolffian duct. 



DISEASES OF THE URINARY ORGANS 



743 



Dunn has found abnormal epithelial structures frequently in the kidney. 
These consist of suprarenal rests, adenopapillary tissue, and papuliferous 
cysts. This finding would help explain the variations seen in Grawitz's 
hypernephroma, since some are distinctly adrenal in character, while 
others show architectural features of carcinomata. The tumor presents 
the appearance of a small lipomatous yellow growth beneath the capsule 
of the kidney, or, more rarely, it may attain considerable size. Histo- 
logically, it consists of epithelial cells arranged in tubules similar to those 
of the cortical portion of the suprarenal capsule. These undergo con- 
siderable fatty infiltration, and almost the entire tumor may be fatty. 
Occasionally active proliferative changes occur in the epithelium, and a 
malignant character is assumed. 

Hypernephroma is very prone to invade the renal vein by extension. 
Epinephrin does not occur in hypernephromata, a fact consistent with 
the theory that they arise from tissue related to the suprarenal cortex. 

Sarcoma of the kidney is a frequent malignant tumor. It may occur 
congenitally, usually as a teratoma or a mixed tumor, or as a simple 




Fig. 349. — Primary sarcoma of the kidney. 



form in later life. The size and general appearance vary considerably, 
but for the most part the structure is soft and grayish or sometimes 
quite red. Extravasations of blood or hemorrhages into the tumor are 
not uncommon. There may be a distinct capsule or the growth may 
be an infiltrating one. Cystic softening is not infrequent (Fig. 349). 

Microscopically, the appearance varies considerably, and the growth 
may be composed of round cells, spindle cells, or cells of various shapes. 
Not rarely a certain number of striped muscle-fibers are found, and to 
such growths the term rhabdomyosarcoma has been applied. In other 
cases there may be embedded in the sarcomatous tissue glandular acini 
composed of cylindrical or irregular epithelium, and to such the name 
adenosarcoma (Wilm's tumor) is given (Fig. 350). Occasionally, myx- 
omatous tissue, smooth muscle-fibers, or even islets of cartilage are 
found. The multiform character of sarcoma of the kidney suggests an 
embryonal origin, and it is not unlikely that inclusions of the primitive 
Wolffian body are the starting-point of the disease. 

The sarcomata of adult life are usually round or spindle celled, 
but angiosarcomata have been seen. 



744 



A TEXT-BOOK OF PATHOLOGY 



Adenoma of the kidney is rare. It originates in the convoluted 
tubules, and presents itself in the form of more or less nodular masses. 




Fig. 35C. — Adenosarcoma or Wilm's tumor of kidney. 



Microscopically, the appearance is that of a tubular adenoma. Pro- 
liferative changes occasionally affect the uriniferous tubules in interstitial 

nephritis, and give rise to small areas 
of adenomatous appearance. In such 
cases, however, the appearances are not 
not those of a tumor in the strict sense. 

Papuliferous cystic adenoma is 
sometimes observed. It occasions tu- 
mors of small or large size with fibrous 
capsules and cystic excavations in 
which the lining epithelium is elevated 
in a papillomatous manner. 

Carcinoma is a rare primary tu- 
mor of the kidney, and occurs in per- 
sons of advanced years. The growth 
begins in the cortical substance or in 
the medulla, and presents itself as a 
soft white or, in case of hemorrhage 
into it, red tumor. 
Microscopically, it is found to be a glandular carcinoma presenting 
acini composed of epithelial cells of various shapes. Metastasis is rare. 




Fig. 351. — Lymphoid infiltrations 
between the renal tubules; from a case 
of leukemia. 



DISEASES OF THE URINARY ORGANS 



745 



Secondary Tumors.— Among the secondary tumors of the kidney 
are both sarcoma and carcinoma. 

In the same group may be included the lymphomatous infiltrations 
of leukemia (Fig. 351). In this disease the kidney is often enlarged, and 
on section is found to be uniformly white or mottled in color, the light- 
colored areas representing masses of lymphoid cells. Most of these 



Fig. 352. — Large retention cyst of kidney (from a specimen in the Museum of the Phila- 
delphia Hospital). 

have doubtless been deposited from the circulation, but there is also 
evidence of local multiplication. 

Cysts of the kidney are of various forms. In the course of chronic 
nephritis, especially the interstitial form, cystic dilatations of the con- 
voluted tubules and Malpighian bodies are observed. These appear 
as small or large rounded bodies lying immediately beneath the capsule, 
and on section are found to contain serous liquid, or colloid material, 
the result of degeneration of the epithelial lining of the cyst. Some- 



746 



A TEXT-BOOK OF PATHOLOGY 



times very large cysts of this character are met with in cases of nephritis 
or even in otherwise healthy kidneys (Fig. 352). Cysts observed in 
kidneys which show no other disease are probably due to undiscovered 
obstructions of the uriniferous tubules. 

Congenital cystic kidneys are of striking appearance. Usually both 
kidneys are affected, and are transformed into masses composed of in- 
numerable cysts varying in size from microscopical points to cavities 
as large as a walnut (Figs. 353, 354). On section, the cysts are found 




Fig. 353. — Congenital cystic kidney (Specimen 2816, Museum New York Hospital). 

to be filled with clear urinous liquid or with colloid material, and be- 
tween them is a stroma of more or less firm fibrous tissue. The pelvis 
of the kidney is usually preserved. These cysts are formed by dila- 
tation of the uriniferous tubules and Malpighian bodies, probably as 
the result of some fetal disease which causes obstruction of the tubules 
at their outlet at the apex of the pyramids, or in consequence of faulty 
union between the upper and the lower segments of the uriniferous 



DISEASES OF THE URINARY ORGANS 



747 



tubules in the development of the organ. Similar cystic degeneration, 
with enlargement of one or both kidneys, may occur in later life. Such 
cystic kidneys have their origin in congenital conditions, even though the 




Fig. 354. — Congenital cystic kidney. 



enlargement does not take place until middle or more advanced age. 
Finally, cystic adenoma may again be mentioned. 

PARASITES 

Bacteria occur in the kidney in various affections: thus pneumo- 
cocci, typhoid bacilli, and the bacilli of glanders and anthrax have been 
repeatedly demonstrated. In pyelonephritis the Bacillus coli communis 
is probably the usual active etiological agent. Streptococci occur in the 
nephritis of septic conditions and in primary infectious nephritis of 
cryptogenic origin. Bacteria are occasionally found in the uriniferous 
tubules without gross lesions of the kidney, and are probably excreted 
with the urine. 

Animal parasites are occasionally observed, such as echinococcus 
cysts, filariBe, the eggs of Fasciola hepatica, amebse, and infusoria. 



748 



A TEXT-BOOK OF PATHOLOGY 



Round-worms and the oxyuris sometimes migrate into the bladder or 
enter through fistula?. 

The echinococcus cyst occurs in the form of hydatids, which may 
perforate into the pelvis of the kidney and discharge with the urine, or 
become inspissated and calcify. The Cysticercus celluloses and Lingva- 
tula rhinaria are extremely rare. The Filaria bancrofti occurs in the 
lymphatic spaces and in the blood-vessels of the kidney in cases of 
filariasis with chyluria. The kidneys in these cases show a waxy appear- 
ance on section, especially toward the apices of the pyramids, and the 
surface of the kidney may be abnormally lobulated. Microscopically, 
the lymphatic spaces about the uriniferous tubules are greatly dis- 
tended. 

The Schistosoma hematobium occasionally produces pyelitis and pye- 
lonephritis, with enlargement of the pelvis of the kidney. 



The Pelvis of the Kidney and Ureter 



CONGENITAL AND ACQUIRED MALFORMATIONS 

Occasionally the pelvis or ureters, or both, may be absent or im- 
perfectly developed. Complete obliteration of the ureter may be ob- 
served. More frequently there are two pelves 
H| or ureters, and when this is the case the mal- 

^ \ formation is, as a rule, bilateral. 

Obstructions of the ureter maybe due 
to twists, to congenital atresia, or to other 
diseases of the ureter, particularly at its en- 
trance into the bladder. It may be brought 
about by the lodgment of renal calculi, by 
tumors of the ureter, or by pressure upon it 
from without. The outflow of the urine may 
be obstructed by diseases of the bladder, and 
particularly by stricture of the ureter. 

Dilatation of the ureter results from the 
conditions just named, and may reach con- 
siderable dimensions (Fig. 355). When the 
obstruction is continued the dilatation may 
affect the pelvis of the kidney as well, and 
eventually the latter may be enormously en- 
larged. The pyramids become flattened, and 
the renal substance may undergo progressive 
atrophy, so that the kidney is converted into 
Fig. 355.— Dilatation of the a S ac-like formation filled with clear liquid, 

ureter due to calculous ob- .-, . . 1 . ,. , , 

struction. partly urine secreted in the earlier stages and 

partly transudate formed after the compres- 
sion has stopped the renal function. To this condition the term hydro- 
nephrosis is applied. 




DISEASES OF THE URINARY ORGANS 



749 



CALCULUS 

Calculi are of frequent occurrence in the pelvis of the kidney, and are 
formed by the precipitation of various normal or abnormal constituents 
of the urine. There may be merely small gritty particles lying in the 
calices or in the pelvis, to which the term renal sand, or gravel, is given; 
or there may be large stones, almost filling the pelvis and calices, and 
forming more or less accurate moulds of these. The most frequent forms 
are those composed of uric acid and oxa- 
late of lime, but phosphate and car- 
bonate of calcium and triple phosphate 
calculi are occasionally found. Stones 
composed of cystin and xanthin are rare. 
Uric-acid calculi are composed of the acid 
itself or of urates, and present themselves 
as yellowish, brownish or red, smooth, or 
somewhat irregular formations. Those 
composed of oxalate of lime are irregular 
in shape and of brownish or red color. 

The results of renal calculi may be 
trivial or serious. Small particles of renal 
sand are frequently passed without serious 
disturbance. Large calculi tend to set up 
inflammation of the pelvis of the kidney, 
and may obstruct the outflow of the urine, 
causing hydronephrosis (Fig. 356). In 
some cases cancer seems dependent upon 
the continued irritation of a retained cal- 
culus. Those in the pelvis or ureter may 
pass down to the bladder, with the clini- 
cal picture of renal colic, or they mav be *"i g . 356 ;~~ Cal S ulus , - in ?W% T 

i . i , . part of ureter and pelvis ol kid- 

caught m the ureter along its course or ney. 
at the bladder opening. If caught, 

ureteritis or hydro-ureter may arise. In its passage the stone may so 
damage the ureter as to cause stricture. 




INFLAMMATION 



Inflammation of the pelvis, or pyelitis, may result from the irrita- 
tion of poisons ingested, such as cantharides, turpentine, and the like, 
or it may occur in the course of infectious diseases of various kinds. 
More frequently it results from the irritation of a calculus, or from 
ascending inflammation consequent upon cystitis and ureteritis. The 
infection passes upward by continuity or along the ureteral lymphat- 
ics; a pericystitis and periureteritis may also lead to a pyelitis. The 
mucous membrane becomes reddened and swollen, and not rarely is 
marked with hemorrhagic ecchymoses. The surface is covered with 
desquamated epithelium and pus-cells. The inflammation may extend 



750 



A TEXT-BOOK OF PATHOLOGY 



to the substance of the kidney {pyelonephritis). Considerable puru- 
lent exudate may take place, particularly when there is a calculus 
partially obstructing the ureter. When there is complete obstruc- 
tion the pelvis may become dilated with pus, and the calices or the 
entire kidney may be converted into a large pus-sac (pyonephrosis). 
Deposits of triple phosphate may occur in pyelitis, and may occasion 
incrustations upon the mucous surface. 

Inflammation of the ureter, or ureteritis, may occur under the same 
conditions as pyelitis. The mucous membrane of the ureter becomes 
swollen and reddened, as in catarrhal inflammations elsewhere, and 
there may be erosions or superficial ulcerations. The other coats are 
thickened by inflammatory infiltration and, in chronic cases, by fibrous- 
tissue overgrowth. 

INFECTIOUS DISEASES 

Tuberculosis of the pelvis of the kidney may occur as a miliary 
tuberculosis, or in the form of caseous nodules or masses. The latter 
may be primary and hematogenous in origin, or may result from ascend- 
ing infection (Fig. 357). It seems from later observations that the 




Fig. 357. — Tuberculous pyelonephritis (modified from Bollinger). 

tubercle bacillus passes up the unobstructed ureter by means of the 
lymphatics in the wall of this tube. When obstructed the passage of 
germs occurs by extension or aided by the changes in pressure between 



DISEASES OF THE URINARY ORGANS 



751 



the bladder and the pelvis because of the impeded downflow of urine 
through the ureter. 

In such instances the mucosa becomes more or less extensively infil- 
trated, and later caseous and ulcerated. The process extends to the 
calices, and subsequently to the pyramids and other parts of the sub- 
stance of the kidneys. The pelvis may contain considerable quantities 
of caseous or puriform matter, and the kidney substance may be ex- 
tensively involved. The urine contains pus-corpuscles and often 




Fig. 358. — Tuberculous nodule in the wall of the ureter, with beginning hydronephrosis 
(from a specimen in the Museum of the Philadelphia Hospital) . 

tubercle bacilli in great numbers. Tuberculosis of the ureters leads to 
nodular or diffuse thickening, and commonly to more or less obstruc- 
tion (Fig. 358). 

TUMORS 

Primary cancer is extremely rare. Secondary cancer may affect 
the pelvis in association with the kidney, or the ureters in association 
with the bladder. Small cystic formations are not uncommonly seen 
in the mucous membranes of the ureters, and may be due to inflamma- 
tory obstruction of the crypts, to proliferation and softening of the 
lymphoid follicles, or to parasitic invasion (psorospermice) . 

PARASITES 

Round-worms have occasionally been found in the ureters. The 
eggs of Schistosoma hcematobium are frequently deposited in the mucous 
membrane, and occasion inflammation and papillomatous excres- 
cences. 



752 



A TEXT-BOOK OF PATHOLOGY 



The Urinary Bladder 
malformations 

Congenital malformations of the bladder are comparatively com- 
mon. Among the more important is exstrophy. The anterior wall of the 
abdomen and of the bladder being wanting, the mucous membrane, with 
the openings of the ureters, is exposed to view. Not uncommonly this 
condition is associated with epispadias, or division of the clitoris. Some- 
times the small intestine discharges through the exstrophic bladder, the 
large intestine being contracted or completely absent. 

Occasionally the urachus remains patulous in consequence of atre- 
sia of the neck of the bladder or urethra, and the urine is discharged 
from the umbilical end. In other cases the urachus is closed at either 
end and the intervening portion is dilated, with the formation of a cyst. 
Again, there may be only partial obliteration of the urachus, the remain- 
ing portion in connection with the bladder being patulous and greatly 
dilated, forming a congenital adventitious sac. In a case known by 
one of us this constituted a cavity of considerable size, and when 
filled distended the abdomen as far as the umbilicus. Congenital di- 
verticula may occur in the anterior wall, and less commonly at the sides 
of the bladder. Complete absence of the bladder, division into lateral 
portions by a septum (vesica bipartitis), and other congenital defects 
are rare. 

Acquired Malformations. — Dilatation of the bladder may result 
from congenital or acquired stenosis of its neck, or of the urethra; or 
from paralysis of its walls, in consequence of disease of the spinal cord 
or nerves. The organ may be greatly increased in size, often reaching 
the umbilicus. When the dilatation is acute the walls are greatly 
thinned, but when it has been gradually developed compensatory hyper- 
trophy of the muscularis and of the submucous fibrous tissues leads to 
thickening of the walls. In these cases the mucous surface presents a 
ribbed appearance, fibrous-tissue bands standing out prominently and 
the mucosa being pouched between the bands. Diverticula of con- 
siderable size may form in this way, and the walls of the bladder some- 
times present a considerable number of pouches. 

CHANGES OF POSITION 

The position of the bladder, or of portions of it, is sometimes ab- 
normal. Thus, it may enter into a hernia, or a part of the wall of the 
bladder may prolapse with the wall of the vagina, forming vaginal 
cystocele. The latter is due to the traction of the prolapsing uterus 
or to repeated overdistention of the bladder, with weakness of the 
anterior vaginal wall. Complete inversion of the bladder through the 
urethra has been observed in women. 



DISEASES OF THE URINARY ORGANS 



753 



RUPTURE 

Rupture of the bladder may be due to traumatism, and particularly 
to perforation by fractured pelvic bones. Rupture from overdisten- 
tion is rare. Occasionally it may result from abdominal compression 
when the bladder is distended with urine, and ulcerative processes be- 
ginning in the mucous membrane may perforate the wall, or phleg- 
monous inflammations or degenerating new growths surrounding the 
bladder may lead to perforation. In women perforations are frequently 
established between the bladder and vagina in consequence of pressure 
of the fetal head or of forceps, and vesicovaginal fistula results. Per- 
foration into the peritoneal cavity is usually followed by fatal acute 
peritonitis. Rupture into the tissues below the peritoneal reflections 
gives rise to widespread infiltration of urine and phlegmonous or gan- 
grenous inflammation. 

CIRCULATORY DISTURBANCES 

Active hyperemia may result from irritant poisons, such as can- 
tharides, or may occur in persons suffering from paraplegia, in conse- 
quence of disturbances of innervation or, possibly, by high acidity of 
the urine. 

Passive hyperemia occurs when there is pressure upon the inferior 
vena cava or thrombosis of that vein. The mucous membrane becomes 
dark red and is often marked with punctate hemorrhages. Consider- 
able varicosity of the veins at the neck of the organ may occur, and may 
give rise to edema, to copious hemorrhages, or to obstruction and reten- 
tion of the urine. 

Hemorrhages in the mucous membrane occur in severe congestion 
or inflammation, and in various hemorrhagic diseases. Large hemor- 
rhages into the cavity itself may result from traumatism from without 
or from calculi. The varicosities before mentioned may occasion con- 
siderable hemorrhage, as may also papillomatous or other new growths. 
Large quantities of blood with little admixture of urine may lead to the 
formation of dense clots within the organ, but when the quantity is 
small the blood is mingled with the urine. 

INFLAMMATION 

Inflammation of the bladder, or cystitis, varies in extent, duration, 
and character. Acute cystitis may result from irritant poisons ex- 
creted with the urine from infectious processes extending from the 
renal pelvis or ureter, and frequently attends acute infectious diseases. 
In these cases, however, the disease is generally mild. More intense 
forms occur from extension of inflammation to the bladder in cases of 
urethritis, or when septic material is introduced in catheterization. 
Retention and decomposition of the urine from strictures or prostatic 
hypertrophy are frequent causes of chronic cystitis. The most common 

48 



754 A TEXT-BOOK OF PATHOLOGY 

organisms in cystitis are micrococci and colon bacilli. These organisms 
may ascend the urethra, descend from the ureter, or extend through the 
neck of the bladder from its related glands. The urine is usually alkaline 
except in cases of colon bacillus infection, when acidity is the rule. 

Cystitis may present itself as a mucopurulent catarrh, acute or 
chronic in course; as phlegmonous inflammation; or as a pseudomem- 
branous process. 

Mucopurulent cystitis in the acute stages causes swelling of the 
mucous membrane, with injection of blood-vessels and sometimes 
punctate hemorrhages. The surface, especially at the base, is covered 
with mucopurulent exudate of a tenacious character, in which pus- 
cells and desquamated epithelium are abundant. The urine tends to 
undergo ammoniacal fermentation. 

In chronic cases thickening of the submucosa and hypertrophy of 
the muscularis cause great thickening of the organ, and the surface 
within is usually ribbed from the prominence of the fibrous-tissue 

bands and the pouching of the mu- 
cous membrane between the bands 
(Fig. 359). Erosion and ulceration 
may occur upon the surface, and 
occasionally perforation of the walls 
takes place. Incrustations of triple 
phosphate and of other common 
salts frequently cover the surface. 

Phlegmonous cystitis results from 
intense infections; infrequently oc- 
curs in the flabby bladder of para- 
plegia when there is retention of 
urine. The submucous tissue is con- 
siderably swollen and infiltrated, and 
complete perforation of the walls and 
paracystitis or phlegmonous inflam- 
mation of the tissues surrounding 
Fig. 359.— Dilated ribbed bladder. the bladder may ensue. 

Pseudomembranous cystitis oc- 
curs in certain severe infectious diseases, and may present itself in the 
form of a typical pseudomembrane, or as a combination of phlegmonous 
and pseudomembranous inflammation. Occasionally, pseudomembranes 
are formed without any inflammatory process in nervous individuals, 
and in the course of or after pneumonia a cast of the entire bladder 
of this nature has been seen by one of the authors. 

Chronic cystitis may follow an acute attack or be primarily a pro- 
gressive process. There is either a hypertrophy of the mucosa, with 
irregular papillomatoid outgrowth, or a thinning of the layer by atrophy. 
The secretion varies, but it is usually mucopurulent and covers closely 
the variegated or uniformly slate-colored mucosa. This color is due to 
altered blood-pigment. The muscular coat undergoes fibrous thicken- 
ing and the contractility is impaired. 




DISEASES OF THE URINARY ORGANS 



755 



INFECTIOUS DISEASES 

Tuberculosis of the bladder is usually secondary to tuberculosis 
of the kidney, or to that of the prostate, seminal vesicles, or epididymis. 
Tuberculous ulcers independent of tuberculosis elsewhere in the uro- 
genital tract may occur in phthisis or intestinal tuberculosis, but such 
cases are rare. The lesions observed in tuberculosis of the bladder are 
ulcerations, beginning in mucosa and submucosa, miliary tubercles for 
the most part occupying the base of the organ and surrounding the 
orifices of the ureters, and there may be distinct or clustered tubercles. 




Fig. 360.— Tuberculosis of the bladder (Orth). 



Numerous small ulcers or a single large ulcerated surface may be ob- 
served (Fig. 360). Deposits of triple phosphate frequently form incrus- 
tations on the surface. 

Syphilitic ulcers and gummata have been observed in the bladder, 
but are extremely rare. 

CALCULI AND FOREIGN BODIES 

The bladder is the commonest seat of urinary calculi. They may 
occur in the form of fine particles or gravel, or as stones of considerable 
size. Usually there is but one; sometimes a considerable number may 
be present. The shape and general appearance depend upon the com- 
position of the stone. 

The formation of calculi is due to precipitation from the urine 
of its various earthy or other constituents as the result of stagnation 



756 



A TEXT-BOOK OF PATHOLOGY 



and fermentative change. Foreign bodies often form the nuclei of stones, 
and thus a calculus in the bladder may form around broken portions of 
catheters, hairpins, or other foreign bodies inserted into the urethra. 
Similarly, parasites may be the nucleus, but in ordinary cases of stone 
mucus or degenerated epithelial cells constitute the focus about which 
the deposit occurs. Catarrhal conditions of the bladder, especially 
when combined with stagnation of the urine as the result of hyper- 
trophy of the prostate, urethral stricture, and the like, are the most 
common antecedent causes. The nucleus being present it attracts 
mucus and other organic matter; this forms a matrix in which salts 
are deposited, probably in some chemical combination with the organic 
matter since they are not found in their ordinary crystalline forms. 

Calculi in the bladder may be composed of uric acid or urates, of 
oxalate of lime, of various phosphates, of carbonate of lime, or of certain 
organic compounds. 

Uric acid and urate calculi are less common in the bladder than in 
the kidney. They result from surcharge of the urine with uric acid in 
lithemic or gouty individuals, and from acid decomposition rendering 
the uric acid and urates insoluble. Uric acid calculi are yellowish or 
red in color, rounded, slightly granular or smooth upon the surface, 
and, as a rule, quite hard. The calculi composed of urates are usually 
more irregular and softer, and are generally lighter in color. Fre- 
quently phosphates are combined with them. These stones may be 
started in the kidney pelvis, especially in the young, and there assume 
somewhat the shape of the kidney hilus. 

Phosphatic calculi may be of several kinds: they may be com- 
posed of phosphate of lime, triple phosphate, or mixed phosphates. 
They form the most frequent variety of calculi and concretions in the 
bladder, and are generally due to alkaline decomposition causing a de- 
posit of the simple phosphate of lime or of the combination of phosphate 
of magnesium with ammonium phosphate, known as triple phosphate. 
These deposits may occur in the form of incrustations upon the surface 
of the bladder in various diseases, or in the form of irregular, soft, and 
more or less white calculi. 

Oxalate of lime occasions rounded, hard calculi, of brownish color 
and of irregular, granular surface, from which they derive the name 
mulberry calculi. They occur in conditions similar to those causing 
uric-acid stones. 

Calculi composed of carbonate of calcium, sulphate of calcium, 
cystin, xanthin, and indigo are extremely rare. 

Results of Urinary Calculi. — While cystitis and retention of urine 
favor calculus formation, the latter is prone to occasion increased irrita- 
tion and inflammation, and may cause serious obstruction to the outflow 
of urine, and thus retention in the bladder. Ulceration may take place, 
and perforation of the bladder-walls may ensue. Hypertrophy of the 
walls occurs when the stone only partially obstructs the outflow, and 
under the same conditions the ureters may become distended and 
hydronephrosis may occur. Not rarely the stone lies in a pouched dila- 



DISEASES OF THE URINARY ORGANS 



757 



tation of the wall of the bladder, either from having been formed in that 
situation in consequence of stagnation of the urine, or from having 
caused a dilatation by weakening the walls at a certain point. Complete 
encapsulation of the stone has been observed in such cases. 

Various objects are found as foreign bodies in the bladder. They 
include most commonly the products of inflammation higher up, such 
as casts or tissue cells, but bodies are sometimes introduced through 
the urethra. Hairpins, tooth-brushes, matches, etc., have been found. 
Occasionally parasites are found in the bladder (filarial and distoma). 

TUMORS 

Polypoid outgrowths from the mucosa may be observed in chronic 
cystitis. 

Papillomata occur either as the result of chronic irritation or as 
apparently causeless tumors. The papilloma presents itself as a some- 
what cauliflower-like elevation affecting the base, and sometimes con- 
siderable portions of the mucosa, and has a whitish or grayish color. 




Fig. 361. — Tuft of papilloma of the bladder. 



It is usually vascular and, therefore, frequently occasions hemor- 
rhages. 

Microscopically, it is composed of a delicate connective-tissue 
stroma containing large, thin-walled blood-vessels, and covered with 
cylindrical epithelium (Fig. 361). Occasionally papillomata become 
transformed into malignant epitheliomatous growths. 



758 



A TEXT-BOOK OF PATHOLOGY 



Carcinoma is a rare form of primary tumor. It occurs as a somewhat 
papillomatous thickening of the mucosa, or as a more considerable in- 
filtration of the wall of the bladder (Fig. 362). Microscopically, it is 
composed of large polymorphous epithelial cells infiltrating the walls 
more or less deeply and irregularly, or arranged in acini or alveolar 
formations. 

Secondary carcinoma of the bladder may result from extension of 
prostatic or uterine cancer. Very rarely the bladder is involved by 
metastasis. 

Fibroma, fibroadenoma, myoma, and myxoma are occasionally 
observed, and cysts may be formed by closure of pouched diverticuli or 



71 




Fig. 362. — A, Epitheliomatous tumor; B, wart-like growths; C, villous growths (Clado). 

by distention of the patulous urachus. Cysts of obscure origin are 
sometimes met with; dermoid cysts are rare. Sarcoma is very rare. 

ABNORMAL CONDITIONS OF THE URINE 

Quantity. — The normal quantity in the adult is from 1500 to 2000 
c.c. Conditions which check the perspiration or action of the bowels 
increase the amount of urine; excessive sweating and diarrhea have the 
reverse effect. In the latter case the excretion may be almost sup- 
pressed (anuria). The same may occur in acute nephritis or chronic 
nephritis with uremia, in extreme anemia, and in acute or chronic 



DISEASES OF THE URINARY ORGANS 



759 



obstructive conditions in the gastro-intestinal tract interfering with 
absorption of water. Occasionally, anuria is reflex, resulting from ob- 
struction of the urinary passages by calculi. The quantity of urine is 
increased (polyuria) in cases of excessive consumption of water, and 
habitually in diabetes mellitus and insipidus and in chronic interstitial 
nephritis. The amount of urine is also influenced by the blood-pressure; 
increased flow follows high arterial pressure, while decrease follows low 
arterial and high venous pressures. 

Specific Gravity. — Normally the specific gravity is 1015 to 1020. 
It becomes increased when the amount of urine is decreased, and 
vice versd. The specific gravity is especially high in diabetes mellitus, 
despite the polyuria, sometimes reaching 1040 or 1050. It is low in 
most forms of chronic nephritis, in diabetes insipidus or simple polyuria, 
and in anemia and hysteria, or other nervous diseases. 

Colors — The normal amber color is due to the presence of various 
pigments, especially urobilin and uro-erythrin. These are derivatives 
of hemoglobin or bilirubin. 

( In pathological conditions other pigments, such as hematopor- 
phyrin, pathological urobilin, melanin, etc., are met with. Indican 
is present in the urine in the form of a chromogen, which may some- 
times become oxidized, with the formation of dark-colored pigment- 
animal-indigo. Certain drugs eliminated with the urine cause dis- 
colorations. Bilirubin occurs in jaundice and other conditions, and 
blood or hemoglobin may cause discoloration. 

Reaction. — The normal reaction is acid, but frequently after meals 
it becomes neutral or even alkaline. The ingestion of certain foods 
rich in alkalies or acids, which become converted into alkaline car- 
bonates (citrates, acetates, etc.), may occasion an alkaline reaction, 
while other acids lead to the opposite result. Decomposition of the 
urine usually causes an intense alkaline reaction by conversion of the 
urea into ammonia. Occasionally the reaction of the urine is ampho- 
teric, both red and blue litmus-paper being acted upon. 

Glucosuria is a term applied to the presence of glucose or grape- 
sugar in the urine. The condition is discussed in the chapter on Dis- 
orders of Metabolism. 

Levulosuria, the presence of fruit-sugar; lactosuria, that of milk- 
sugar; and dextrinuria, that of dextrin in the urine, have been dis- 
covered. 

Pentosuria is a condition in which pentoses, sugars containing five 
atoms of carbon in each molecule, appear in the urine. The condition is 
important mainly because pentoses, react to certain reduction tests 
(Fehling's, Trommer's) like glucose. They do not polarize light nor 
ferment as does glucose. Pentosuria is a metabolic disorder of uncertain 
character sometimes occurring independently, sometimes in association 
with diabetes. It is not the result of disordered metabolism of starches, 
and the source of the pentoses is uncertain, though it is not improbable 
that they are derived from nucleoproteins of various organs; being there- 
fore endogenous, since they may be excreted in quantity greater than 



760 



A TEXT-BOOK OF PATHOLOGY 



present in the food, and such patients seem to have a tolerance to the 
ingestion of pentose. 

Alkaptonuria is a metabolic disturbance in which the urine turns 
black after excretion. The addition of alkalies to the fresh urine causes 
immediate change to a dark or black appearance. The chemical sub- 
stances concerned in this phenomenon are homogentisic acid and some- 
times uroleucinic acid, aromatic acids derived from protein metabolism. 
These substances are in part derivatives of albumins of the food, but 
always also in part the products of metabolic destruction of tissue 
proteins. Their appearance in the urine has been ascribed to the lack 
of ferments which normally destroy these substances. It has also been 
held that homogentisic acid is formed in the intestines by bacterial 
processes involving decomposition of tyrosin. Clinically, alkaptonuria 
has been found associated with diabetes, tuberculosis, and pyonephrosis. 
In a number of cases of alkaptonuria there has been found the peculiar 
black pigmentation of cartilages called by Virchow ochronosis. This at 
times affects superficial cartilages like those of the ear, where it causes 
visible discoloration. Besides alkaptonuria, chronic phenol-poisoning 
may also occasion ochronosis. 

Choluria is the name indicating the presence of biliary pigments 
and acids in the urine. It is most frequently observed in cases of 
jaundice due to hepatic disease, but may also occur in so-called hema- 
togenous jaundice, the formation of the pigment in some of the latter 
cases probably taking place in the kidneys themselves. The urine pre- 
sents a dark color, varying from brownish to greenish. Oxidizing sub- 
stances, such as fuming nitric acid, produce a play of colors. 

Microscopically, the cellular constituents of the urine are found 
stained, and granular concretions of bilirubin or rhombic crystals may 
be observed. Hyaline casts, more or less deeply stained by the pigment, 
are frequently seen. 

Urobilinuria. — Urobilin occurs in the normal urine mainly as a 
chromogen, or is converted into urobilin on the addition of acid. Some- 
times urobilin is present in large quantities in the fresh urine. This 
has been particularly observed in fevers, in jaundice, and in certain 
anemic diseases, especially in pernicious anemia. Its presence in large 
quantities is due to damage to the liver parenchyma. 

Indicanuria. — Indigo-blue occurs in the urine as a chromogen 
which gives rise to the formation of indigo on decomposition. This 
indican, or indoxyl sulphate, is a product of indol derived from the in- 
testine, and an excess of indican in the urine is significant of intestinal 
decomposition. 

Other forms of the ether-sulphuric-acid series occur in the urine, but 
are less significant. 

Acetonuria occurs to a slight extent in health, but more particu- 
larly in conditions of inanition, in gastro-intestinal disturbances, and 
in fever. It is especially significant in diabetes mellitus, and may become 
very pronounced toward the latter end of this affection. 

Diaceturia, or the condition in which diacetic acid appears in the 



DISEASES OF THE URINARY ORGANS 



761 



urine, is also met with in fevers and inanition, but particularly in 
diabetes. 

Lipaciduria refers to the presence of fatty acids in the urine, but 
has no special significance. 

Hydrothionuria refers to the presence of sulphuretted hydrogen 
in the urine. This is noted occasionally in auto-intoxications or as the 
result of fermentative changes in the urine. The urine may have a 
foamy appearance, to which the term pneumaturia is sometimes ap- 
plied. Other gases may be present, but only in small proportion and 
rarely. 

Melanuria is a term applied to the dark discoloration of the urine 
occasionally seen in persons suffering from pigmented tumors. It also 
occurs in phthisis and other wasting diseases. As a rule, the urine be- 
comes darker after addition of oxidizing substances, but it may be quite 
dark when passed. It contains iron and sulphur. 

Albuminuria. — Minute traces of serum-albumin probably occur in 
the normal urine. The term "albuminuria," however, is applied to cases 
in which albumin is readily detected. It may be accidental — that is, 
dependent upon the admixture of albuminous substances from the 
mucous membrane lining the urinary passages — or essentially renal in 
character. In the former instances the presence of abundant blood- or 
pus-cells indicates the nature of the case. True renal albuminuria con- 
sists of the excretion with the urine of serum-albumin and serum- 
globulin, the former being considerably more abundant than the latter. 
Pure serumuria is extremely rare, and pure globulinuria perhaps even 
more so. 

Albuminuria is more frequently the product of actual renal disease 
or nephritis, and is then due to the disease of the epithelium of the 
glomeruli and tubules. A certain amount of albumin occurs in de- 
generative or congested conditions of the kidneys; in various general 
diseases affecting the blood without manifest disease of the kidney, 
such as anemias, diabetes, toxemias, and the like; in certain nervous 
affections probably influencing the circulation; and in disorders of the 
digestive tract. 

At times albuminuria is periodic or cyclic, this periodicity depend- 
ing upon general conditions, such as diet, exposure, and exercise, which, 
in turn, affect the blood or renal circulation. Considerable amounts of 
albumin in the urine are never physiological. Large proportions of 
globulin occur in amyloid disease of the kidneys. 

Albumosuria. — Various albuminous substances derived from serum- 
albumin or serum-globulin, and not coagulable by heat, occur in the 
urine. These are hydration products designated albumoses or pro- 
pepton. True pepton has never been found in the urine. Albumo- 
suria occurs in cases in which pus-cells or large exudates are undergoing 
absorption, as in septic processes, pneumonia, and the like {pyogenic 
albumosuria). In another group of cases intestinal malassimilation or 
decomposition comes into play (enterogenic albumosuria). In the third 
group diseases of the blood, such as leukemia and various intoxications, 



762 



A TEXT-BOOK OF PATHOLOGY 



are active (hematogenic albumosuria). A fourth, or puerperal, form 
occurs after labor. In the "albumosuria" of Bence-Jones, which accom- 
panies myelomata, the abnormal substance is probably not an albumose, 
but a simple albumin. 

NucIeo=aIbuminuria. — Nucleo-albumin, formerly supposed to be 
mucin, is derived from the protoplasm of the surface epithelium of the 
urinary tract, and occurs in the urine in small quantity in nearly all 
persons, and in large quantity when there is irritation of the lining 
mucosa, particularly in pyelitis and cystitis. 

Cystinuria is a disorder of metabolism in which cystin, a nitrogenous 
sulphur compound, appears in the urine. Cystin is a normal inter- 
mediary product of metabolism which is further oxidized and, there- 
fore, does not appear in the urine. In cystinuria there is a retardation 
or absence of this oxidation. In some cases diamin, putrescin, and 
cadaverin have been found associated with cystin. This appears to 
represent an advanced grade of the same metabolic disturbance. Cysti- 
nuria may occasion no symptoms; but sometimes cystin calculi are 
formed in the kidney or bladder. 

Fibrinuria occurs in conditions in which lymph or blood gains ac- 
cess to the urinary passages. Fibrinous casts or shreds may be passed, 
or small flocculent particles are observed. Fibrinuria is usually asso- 
ciated with hematuria or chyluria. 

Hematuria is a term applied to the presence of blood in the urine. 
This may be accidental from admixture of menstrual blood and the 
like, or may be a pathological condition, in which the blood originates 
from the kidneys, ureters, bladder, urethra, or other parts of the urinary 
system. Renal hematuria may result from intense congestion or from 
hemorrhagic nephritis. Traumatism, either from without or from 
calculi in the pelvis, is a frequent cause. Tumors and specific inflamma- 
tory processes are occasional causes. Sometimes hematuria is due to 
intense anemia, hemorrhagic diseases, or severe intoxications. Hema- 
turia which is due to admixture of blood with the urine below the 
kidney results from traumatism, injury by calculi or catheterization, 
from vascular tumors, and occasionally from inflammatory or other 
disease processes. 

Renal hematuria is distinguished from that originating in the 
bladder by the intimate admixture of urine and blood, and by the 
associated evidences of renal disease — renal epithelium, tube-casts, etc. 
Fragmentation of the red corpuscles is said to indicate renal hematuria. 
In hematuria originating in the bladder larger clots may pass, in associ- 
ation with bladder epithelium and mucin (nucleo-albumin). In cases of 
sudden renal hemorrhage large clots, sometimes forming casts of the 
pelvis, may be formed and discharged. 

Hemoglobinuria indicates the presence of free hemoglobin or of 
methemoglobin in the urine, without the presence of blood-corpuscles. 
Hemoglobinuria results from causes which lead to disorganization of 
blood and elimination of the coloring-matter through the kidneys. It 
is met with in various infectious diseases, such as malaria, and in in- 



DISEASES OF THE URINARY ORGANS 



763 



toxications, as in poisoning with potassium chlorate, carbolic acid, 
arsenic and other drugs, or with toadstools. It occasionally results 
from snakebite or poisoning by other venomous animals. 

Paroxysmal hemoglobinuria is a form of intermittent disease espe- 
cially frequent in subtropical countries. The attacks sometimes seem 
to be determined by exposure to cold and other external influences, 
while the predisposition may be dependent upon syphilis or other 
general disorders. The urine presents a dark-red or brownish color, 
and when tested with the spectroscope shows the bands indicative of 
hemoglobin or methemoglobin. 

Microscopically, the hemoglobin may present itself in the form of 
granules or cast-like formations, or sometimes as crystals. Blood- 
corpuscles are absent or, at most, present in extremely small numbers. 

Lipuria. — A small amount of fat may appear in the urine in cases 
of advanced diffuse nephritis with fatty degeneration, and in certain 
cases of pyelitis. In other cases lipuria results from disorders in which 
there is excess of fat in the blood (lipemia). This occurs in cases of ex- 
cessive consumption of oil or fatty food and in cases of intoxication, 
notably by arsenic. It is sometimes present in diabetes, phthisis, 
chronic alcoholism, and obesity, and fractures injuring the marrow or 
serious traumatism of the subcutaneous fatty tissues may cause fat 
embolism and lipuria. 

The appearance of the urine varies with the amount of fat, but, 
as a rule, there is a solid scum upon the surface, and there may be large 
oil-drops. Occasionally the urine is quite milky when recently passed. 
Microscopically, oil-drops are more or less abundant, and fat-crystals 
may be discovered. 

Chyluria is the name applied to a milky condition of the urine 
which probably results from admixture of lymph or chyle. The urine 
is light colored, and more or less milky in appearance. Often there is a 
reddish discoloration from associated hematuria (hematochyluria). 
The urine contains albumin and sometimes albumoses. 

Microscopically, numerous oil-drops of varying size and, usually, 
blood-corpuscles are detected. The most frequent cause is the obstruc- 
tion of the lymphatic channels and their subsequent rupture in the 
kidney or bladder in consequence of the lodgment of the Filaria 
sanguinis hominis. In these cases the embryos of the filariae are usually 
detected in the urine. Sometimes a chyluria is non-parasitic, but the 
causes are obscure. 

Bacteriuria. — Normally, the urine contains no bacteria. In cases 
of cystitis or other inflammatory diseases, however, and particularly 
when catheterization has been practised, bacteria of decomposition 
may be present, such as the Micrococcus ureoe, Bacterium termo, the Bacil- 
lus proteus, yeast fungi, and other forms. Not rarely the Bacillus coli 
communis is met with, particularly in ascending infections of the urinary 
tract. In cases of certain infectious diseases, such as typhoid fever, 
pneumonia, and erysipelas, the specific micro-organisms may be found 
in the urine, having escaped from the blood through the capillaries of 



764 



A TEXT-BOOK OF PATHOLOGY 



the glomeruli. Streptococci are also met with in primary and secondary 
infectious nephritis. Pseudodiphtheria bacilli are so common upon 
the genitalia and in the urethra that it is common to find them in 
voided urine. The tubercle bacillus may be discovered in cases of 
tuberculosis of the kidney, ureters, bladder, or other parts of the uri- 
nary tract (Fig. 363). It is frequently present in clusters, this consti- 
tuting a marked point of distinction from the smegma bacillus, which 
is often found in urine, especially that of women, and is easily mistaken 
for the tubercle bacillus. Another point of distinction is the greater ease 



Fig. 363. — Tubercle bacilli in the urine; from a case of tuberculous cystitis (Jakob). 

with which the smegma bacillus, stained with carbolfuchsin, may be 
decolorized by alcohol. Positive differentiation in doubtful cases is 
made by injection of the urine into guinea-pigs. 



The various inorganic and organic constituents of the urine may 
be present in excessive quantities, and may form deposits, or abnormal 
chemical substances may be detected. 

Uric acid is deposited in the form of yellowish, brownish, or reddish 
crystals of whetstone shape, or as irregular angular formations super- 
imposed or clustered together (Fig. 364). The color is due to uro-ery- 
thrin taken up from the urine. The crystals of uric acid may deposit 
from a highly acid urine, even though there be no excess. 

Oxalate of lime occurs in the form of highly refracting octahedral 
corpuscles, their appearance being likened to that of an envelope 
(Fig. 365). Certain foods rich in oxalates may cause excessive excretion, 
and oxaluria occurs as an independent condition of obscure nature 
allied to gout and lithemia. Oxalates deposit from highly acid urine, 
even though no excess be present. This must be distinguished from 
oxaluria proper. 

Phosphates. — Various forms of phosphates are found in crystalline 
form in urinary sediments. Basic phosphate of magnesium and neutral 




CHEMICAL CHANGES AND SEDIMENTS 



DISEASES OF THE URINARY ORGANS 



765 



phosphate of lime are found in urine becoming alkaline, while the phos- 
phate of ammonium and magnesium, or triple phosphate, is met with 
when alkaline decomposition takes place. It presents itself in different 
forms, the most characteristic being the large coffin-lid crystals and 
certain star-shaped formations (Fig. 366). Triple phosphate is espe- 




Fig. 364. — Various forms of uric acid crys- Fig. 365. — Various forms of crystals of 
tals. oxalate of calcium. 



cially abundant in cystitis with alkaline decomposition of the urine in 
the bladder. 

Urates are deposited from acid urines as a whitish or reddish sedi- 
ment of amorphous character. The reddish color sometimes observed 
is due to admixture of urinary pigment. In decomposing urine, of 




Fig. 366. — Crystals of triple phosphate Fig. 367. — Urate of ammonium crystals, 
(ammonium-magnesium phosphate). 

somewhat alkaline reaction, urate of ammonium is deposited as hedgehog 
crystals or masses (Fig. 367). 

Hippuric acid is rarely met with, excepting after the ingestion of 
benzoic acid or of certain fruits. It forms long, prismatic crystals, which 
occur in groups. 



766 



A TEXT-BOOK OF PATHOLOGY 



Carbonates and sulphates are rarely observed in urinary sediments. 

Fat=crystals occur in the form of fine needles, or of aggregations 
arranged in a star-like manner and resembling tyrosin groups (Fig. 368). 
They are found in cases of chronic nephritis, pyelitis, and cystitis. 

Tyrosin. — This substance usually occurs in the urine in solution, 
or rarely in the form of sheaves composed of fine needles arranged in 
star-like clusters (Fig. 368). 

Leucin occurs as small spheres, often having a somewhat radiated 
structure within. These are most readily discovered when the urine 
has been partially evaporated. 

Leucin and tyrosin are observed in acute yellow atrophy of the liver, 
in phosphorus-poisoning, and occasionally in severe infectious fevers. 




Fig. 368. — Leucin spheres and tyrosin Fig. 369. — Cholesterin plates and fat- 
needles, crystals (needles). 



Cystin occurs in the form of hexagonal plates often superimposed. 
They are most frequently associated with cystin calculi in the kidney. 

Xanthin is extremely rare, but may be associated with xanthin 
calculus. 

Cholesterin appears in the form of flat, quadrilateral plates, with 
a re-entering angle at one of the corners (Fig. 369). They are met with 
in old cystitis or pyelitis, but are rare. 

Indigo. — Amorphous particles or crystals of indigo may be found 
in urine containing great excess of indoxyl sulphate. They present a 
characteristic bluish color. 

Bilirubin, hemoglobin, methemoglobin, and hematoidin are occa- 
sionally seen as brownish granular concretions or in the form of rhombical 
crystals. (See Chyluria, Hemoglobinuria.) 

The Urethra 

congenital abnormalities 

Absence of the urethra is sometimes met with in association with 
other defects of development. Partial deficiencies and abnormal struc- 
ture of the urethra are more frequent. Thus in the female it may be 
reduced in length and open in the anterior wall of the vagina, and in the 



DISEASES OF THE URINARY ORGANS 



767 



male may terminate at the base of the scrotum. Obliteration of part of 
the urethra (atresia) may occur in cases of defective development of the 
corpus spongiosum; more commonly there is obliteration of the meatus. 
Other abnormal conditions will be considered in connection with defect- 
ive development of the penis. 

INFLAMMATIONS 

Inflammation of the urethra, or urethritis, is most frequently due 
to a specific micro-organism — the gonococcus of Neisser. Some cases, 
however, are non-specific, resulting from irritation by chemical or 
mechanical agents with associated infection (staphylococci, streptococci, 
or other organisms). Some of these cases are caused by direct trauma- 
tism, as by blows, injuries caused by catheterization, and the like; 
in other cases foreign bodies, as calculi, become lodged in the urethra 
and occasion inflammation or injure the urethra in passing. Urethritis, 
like inflammations of other mucous membranes, may occur in various 
infectious diseases, such as typhoid fever, scarlet fever, small-pox, etc. 
In the female, inflammations of the vagina and vulva frequently ex- 
tend to the urethra. A form of pseudomembranous urethritis of obscure 
origin has been observed in a few cases. 

Specific urethritis, or gonorrhea, is always due to direct infection 
with the gonococcus (for description of the organism, see Part I). 
Certain conditions of the urethra favor infection; thus an adherent 
prepuce, by causing greater retention of the infective matters, increases 
the liability, and probably congested and irritated states of the urethral 
mucosa heighten the susceptibility. The vulnerability of different indi- 
viduals probably varies; and doubtless the micro-organism has greater 
virulence in some instances than in others. 

Pathological Anatomy. — Urethritis usually first affects the mucosa 
at or near the meatus, but tends to spread rapidly to the posterior parts. 
The mucosa is at first intensely congested, red, and swollen. Soon a 
purulent exudate, of yellowish or greenish color, makes its appearance. 
The small crypts or lacunae swell and become distended with purulent 
exudate. 

Microscopically, urethritis presents the features of an intense puru- 
lent catarrh. Within a few days of the onset the superficial epithelium 
becomes loosened and begins to desquamate; and at the same time 
polymorphonuclear leukocytes make their way to the surface between 
the epithelial cells. The pus-cells and epithelium of the surface exudate 
contain gonococci in abundance, and the organisms are discovered in the 
cells and to a less extent between the cells of the deeper layers of the 
mucosa (Fig. 370). The process extends most deeply in those parts of 
the urethra (penile portion) in which the lining epithelium is of the 
columnar variety. 

Associated Lesions. — In simple cases the disease proceeds no further 
than has been described, but after a period of several weeks gradually 
subsides. Very frequently, however, the inflammation extends in 



768 A TEXT-BOOK OF PATHOLOGY 

various directions, and complicating conditions arise. Sometimes the 
infective agents penetrate the membrana propria of the small glands 
(Littre's glands), or enter the submucosa by direct invasion through the 
interglandular parts of the mucosa. Leukocytic collections in the 
submucosa or periurethral abscesses may result. In these cases the 
gonococcus alone may be the infective cause, or other pyogenic organ- 
isms may be associated; sometimes periurethral lesions are caused by 
staphylococci independently of gonococci. Occasionally, accumulations 
of pus in Tyson's glands may simulate periurethral abscesses. In the 
female, similar purulent distention of the glands of Bartholin is a fre- 
quent lesion. The inflammation of the urethra is often confined to the 
anterior portion {anterior urethritis), but may extend to the posterior 




Fig. 370. — Acute urethritis, showing purulent infiltration and gonococci in the cells and 
between the cells (Birch-Hirschfeld). 

portion {posterior urethritis). In the male, secondary involvement of 
the prostate gland is likely to occur with posterior urethritis; and, 
more rarely, the organisms invade the vas deferens and find their way 
to the epididymis, causing acute epididymitis. The bladder is rarely 
involved, the mucosa apparently offering considerable resistance to the 
infection. In the female, acute vaginitis, and especially inflammation 
of the cervix uteri, are commonly associated. Secondary extension to 
the uterus may occasion gonorrheal endometritis; more frequently the 
uterus is but little affected, while the Fallopian tubes suffer intense in- 
flammation. Catarrhal or purulent salpingitis, often complicated with 
local peritonitis, is one of the most important of the complications. 
When pus from a gonorrheal urethritis is brought in contact with the 
conjunctiva a severe form of purulent conjunctivitis results. 



DISEASES OF THE URINARY ORGANS 



769 



Metastatic lesions are not infrequent. Among these, gonorrheal 
arthritis is the most familiar. It usually occurs late in the disease, some- 
times after an interval of weeks or months from the onset, and involves 
the larger joints (knee, elbow, wrist). Purulent exudation and fibrous 
ankylosis may result. A similar lesion is gonorrheal tenosynovitis. 
Sometimes the pericardium, endocardium, and myocardium are in- 
volved; and, more rarely, the pleura and the membranes of the cord. 

Enlargement of the lymphatic glands of the inguinal region (bubo) 
is frequent; sometimes it terminates in suppuration. 

Chronic urethritis is usually the result of continuation of the acute 
form. It may present itself in the form of a chronic catarrhal process, 
as a hyperplastic inflammation, or as a productive or cicatrizing form. 

In the catarrhal form of chronic urethritis the lesion is practically 
the same as in the acute disease. The epithelium is loosened and more 
or less desquamated, and sometimes distinct erosions are observed. 
Definite ulcerations may occur in parts back of strictures. The columnar 
epithelium may be converted into the squamous form diffusely or in 
localized areas. The crypts and glands of the mucosa may be distended 
with desquamated cells and more or less periglandular inflammation may 
be observed. 

In the hyperplastic variety the mucosa is thickened in a papilloma- 
tous manner, and diffuse catarrhal inflammation is associated. 

The productive or cicatrizing form is the most important. It may be 
diffuse in character, but is usually localized and leads to stricture 
formation. 

Stricture of the urethra is most frequent in the membranous por- 
tion, but may occur in the anterior parts. Not rarely there are several 
strictures in the course of the canal. Histologically, the stricture is the 
result of productive inflammation of the mucosa and submueosa. It is, 
therefore, a lesion of slow development, and may not become obstruc- 
tive for months or years after the acute attack of gonorrhea, to which 
it owes its origin, has subsided . The lumen of the urethra is encroached 
upon in limited area or for a considerable distance, and, on section, the 
stricture is found to be hard and resisting. When the lumen of the 
urethra is greatly narrowed the outflow of urine is impeded, and hyper- 
trophy of the walls of the bladder results. Later, dilatation of the 
bladder, and even of the ureters and pelvis of the kidneys, may result. 
The urethra back of the stricture frequently presents the lesions of 
chronic catarrhal or hyperplastic urethritis, the obstruction serving 
to prolong the original inflammation of these parts. Rupture of the 
urethra and extravasation of urine into the cellular tissues, with subse- 
quent necrosis and gangrene, may occur. 

In chronic urethritis there is usually a constant but slight dis- 
charge of mucous exudate (gleet). Examination of this may discover 
no gonococci or only an occasional group. The urine contains floccu- 
lent shreds (clap-threads), which on microscopical examination are 
found to be granular or homogeneous structures resembling cylindroids, 
and often covered with pus-cells that have adhered to the surface. The 

49 



770 



A TEXT-BOOK OF PATHOLOGY 



amount of discharge may be quite copious at times, especially in the 
hyperplastic and catarrhal forms of chronic urethritis. 

, INJURIES OF THE URETHRA 

The urethra may be injured by traumatism from without or within. 
In cases of falls with injury of the perineum the membranous portion 
of the urethra may be seriously lacerated, and in women injuries sus- 
tained during labor may cause immediate rupture of the urethra, or may 
first occasion inflammatory and necrotic changes in the anterior wall 
of the vagina and secondary perforation of the urethra. Injuries from 
within the urethra may be due to forced attempts at catheterization 
when some form of obstruction opposes the passage of the instrument. 
"False passages" are thus occasioned, and may result in fistulae and ex- 
travasations of urine. Concretions or calculi from the kidney or bladder 
may lodge in the urethra, and may cause immediate perforation or 
primary inflammation, with secondary rupture of the walls. 

Rupture of the urethra causes extravasation of urine into the peri- 
urethral cellular tissues. If the skin is intact and the urine cannot 
escape, widespread inflammation, necrosis, and gangrene are liable to 
occur. Fistulous communications may be established with the exterior, 
or, in women, with the vagina. 

INFECTIOUS DISEASES 

Gonorrheal urethritis is the important infectious disease of the 
urethra. For convenience it has been described under Inflammations. 

Tuberculosis of the vesical end of the urethra may be associated 
with tuberculosis of the bladder. Lupus sometimes involves the meatus 
and anterior end of the urethra in cases of lupus of the external geni- 
talia of women. Very rarely tuberculosis of papillary form is met with 
in the urethral mucosa. 

Syphilis. — The chancre may occur in anterior parts of the urethra 
in either sex. It usually undergoes rapid ulceration. Mucous patches 
may occur within the meatus. 

TUMORS 

The urethra of women is more often the seat of tumors than is that 
of men. 

Small polypoid tumors are occasionally seen hanging from the 
meatus; they may be fibrous, villous papillomata, or glandular, the 
latter tending to become cystic. 

Carcinoma is usually secondary to cancer of the external genitalia 
(vulva, vagina, glans penis). Primary carcinoma originating from 
Cowper's gland has been described, and a few cases of carcinoma of 
other parts of the urethra have been observed. 

Cysts of the mucous membrane, due to retention of the contents 
of the small glands, are occasionally met with, especially in the posterior 
portion of the urethra. The inner lining of the cyst is elevated in the 
form of papillae covered with squamous epithelium. 

Sarcoma of the urethra has been described, but is very rare. 



CHAPTER VIII 



DISEASES OF THE REPRODUCTIVE ORGANS 



The Uterus 

Development and Anatomy. — The uterus is formed by the fusion 
of the middle portions of Muller's ducts, the fusion first occurring be- 
low where the cervix uteri is developed. The epithelial lining of the 
ducts gives rise to the mucosa of the uterus, and its outer layers, to the 
muscularis. The utricular glands are developed by ingrowths from the 
lining cells, and first appear and reach their most complex development 
in the cervical portion. The outer surface of the cervix (portio vaginalis) 
is lined with stratified squamous epithelium; the cavity of the uterus 
and cervical canal, with cylindrical ciliated cells. In the cervical por- 
tion are found numerous racemose glands and between them simple 
tubular glands; in the corpus uteri the glands are simple tubules. 



CONGENITAL ABNORMALITIES 



Absence of the uterus is very rare. The organ, however, may be 
represented only by a mass of rudimentary tissue. Hypoplasia of the 
uterus may be a congenital condition, or may be the result of arrested 
development and the consequent failure to increase in size at the age 





Fig. 371. — Uterus bicornis unicollis (Winckel). 



of functional activity. The term uterus infantilis is applied. Stenosis 
and atresia of the uterus and vagina may be the result of disease or mal- 
developments, due to partial obliteration of Muller's ducts. 

Among the more striking malformations of the uterus are those which 
result from incomplete fusion of Muller's ducts. In normal develop- 
ment these ducts unite and fuse in the lower portion to form the uterus 
and vagina, but remain separated above, where they form Fallopian 
tubes. Among the anomalous conditions of the uterus are uterus 
bicornis, in which the cervical portion of the uterus is single and two 
entirely distinct uterine cornua are present (Fig. 371); uterus septus, 

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A TEXT-BOOK OF PATHOLOGY 



in which the external appearance may be that of a single uterus, but on 
section a septum is discovered, which divides the organ into lateral 
halves (Fig. 372) ; uterus duplexus, in which there are two vaginas, two 
uteri, but only two fallopian tubes. The term uterus unicornis is used 
to designate cases in which but one of Miiller's ducts has developed, 
the other remaining rudimentary. Malformations of the vagina may 



be associated with those of the uterus already named, though this is 
rarely the case. A number of subdivisions have been distinguished for 
each of these malformations, but they are unimportant. 



The normal position of the uterus is one of slight anteversion with 
anteflexion; that is, the fundus lies a little farther to the front than the 
cervix, and there is a slight bend or flexure in the middle portion. 

Anteflexion is a condition in which there is marked angulation of 
the uterus, the fundus falling forward. Shortness of the round ligaments 
predisposes to this condition; and it may be caused by the pressure of 
tumors situated posteriorly, by distention of the rectum with gas, by the 
traction of adhesions and by abnormal conditions of the uterus itself, 
causing a loss of tone in the walls. The grade of anteflexion varies 
greatly. Among the effects of this condition is interference with the 
discharge of menstrual blood, with consequent accumulation and in- 
tense dysmenorrhea. 

Anteversion, or the tilting forward of the uterus without abnormal 
angulation, occurs under similar conditions, but is less important. 

Retroflexion of the uterus occurs in cases in which the walls of the 
uterus are abnormally soft and have lost their tone. It may be caused 
by the pressure of tumors or the traction of adhesions. Sometimes it is 
due to habitual constipation, causing pressure upon the lower part of 
the uterus (cervix) by masses in the rectum; retroversion and subse- 
quently retroflexion are produced. Laxness of the vaginal walls and 




Fig. 372. — Uterus septus (Cruveilhier). 



ALTERATIONS OF POSITION 



DISEASES OF THE REPRODUCTIVE ORGANS 



773 



rupture of the perineum may cause this or other abnormal positions of 
the uterus by depriving the organ of its support from below and sub- 
jecting it to the unresisted pressure of the abdominal viscera. The 
degree of retroflexion varies from slight angulation to a complete back- 
ward doubling of the organ. The fundus may undergo considerable con- 
gestion from the interference with circulation, and it is not rarely en- 
larged. Adhesions between the uterus and rectum are frequent. 

Retroversion is the condition in which the position of the uterus 
is changed in relation to the pelvis and soft parts, with or without 
flexion or alteration in the angle of the various sections of the organ 
itself. The same causes are operative as for flexion, especially prominent 
being subinvolution. 

Lateral displacements of the uterus are rare, and are associated 
with adhesions or tumors operating laterally. 

Upward dislocation may be caused by pressure of tumors in the 
pelvis; it may be due to the traction of adhesions between the uterus and 
large tumors of the ovary. In such cases the uterus may be greatly 
stretched and the vagina may be similarly affected. 

Prolapse of the uterus is a term applied to descent or downward 
displacement. It is possible to distinguish any number of degrees of 
prolapse, but it is sufficient to speak of two only: incomplete prolapse, 
in which the os uteri is still within the vagina (procidentia) ; and complete 
prolapse, in which it projects through the vulva, thus partially or wholly 
everting the vagina. The causes of prolapse of the uterus are numerous. 
Injuries to the perineal floor and unusual laxity of the vaginal walls or 
the ligaments of the uterus are very important. Traumatism and ex- 
cessive pressure upon the uterus from the abdomen may cause descent 
of the organ, especially if laxity of the ligaments was present before. 
Retroversion also favors the descent by bringing the uterus into the 
pelvic axis. Enlargement of the uterus itself may be the cause of pro- 
lapse, and in any case the organ usually becomes enlarged after the 
prolapse, in consequence of passive congestion. The cervix is gener- 
ally directed somewhat backward, and the mucous membrane fre- 
quently presents catarrhal inflammation and contains enlarged veins. 
The cavity may be filled with considerable mucous secretion. 

In some instances of apparent complete prolapse the fundus of the 
uterus may be but little displaced, the great descent of the os uteri in 
such instances being due to hypertrophic elongation of the vaginal portion 
of the cervix. 

In all cases of prolapse the anterior and posterior walls of the vagina 
are displaced downward more or less, and sometimes may be completely 
everted. The anterior vaginal eversion may draw with it the posterior 
wall of the bladder, and cystocele results. Similarly, the posterior vag- 
inal wall may drag down the anterior wall of the rectum, and rectocele 
is produced (Fig. 373). 

Inversion of the uterus is a condition in which the organ is turned 
inside out to a greater or less extent. This condition is caused by traction 
upon the placenta during rapid labor, or in the presence of lax uterine 



774 



A TEXT-BOOK OF PATHOLOGY 



muscle, when it is acutely developed; or by the similar traction of poly- 
poid submucous tumors, when it is more slowly formed (Fig. 374) . There 




Fig. 373. — Complete prolapse of the uterus (Penrose). 




Fig. 374. — Fibroid polyp, producing partial inversion of the uterus (Penrose). 

may be only a slight inversion of the fundus, or the organ may be com- 
pletely inverted and may present itself through the vagina and vulva. 



DISEASES OF THE REPRODUCTIVE ORGANS 



775 



This may be associated with partial or complete prolapse. Secondary 
changes are apt to occur in such cases. The mucous membrane suffers 
catarrhal inflammation with ulceration; and the entire uterus, though 
at first perhaps enlarged by congestion, subsequently atrophies. 

STENOSIS, DILATATION, AND RUPTURE 

Stenosis of the uterine cavity may occur as a congenital condition, 
or may be acquired in cases in which inflammation has led to cicatricial 
stricture. There may be almost complete obliteration of the external 
or internal os uteri. 

Dilatation of the cavity of the uterus is a not infrequent result of 
stenosis. The dilated cavity may be filled with mucous or seromucous 
secretion from the non-menstruating mucous membrane (hydrometra) , 
or with accumulations of menstrual blood (hematometra). Occasionally, 
in cases of hydrometra secondary decomposition of the liquid causes 
gas formation, and physometra results, or suppuration occurs (pyometra). 
In cases of hematometra the amount of blood in the uterine cavity may 
be very considerable, and in some instances rupture of the wall of the 
uterus is the result. This may be simply due to the increasing pressure, 
or it may result from inflammation or ulceration at the point of stenosis. 

Rupture of the uterus may occur during pregnancy or labor; and 
occasionally at other times in consequence of inflammations, abscess, 
softened tumors, and the like. The commonest ruptures are, of course, 
those in and near the cervical part, but during severe labors, especially 
of the more difficult presentations, the musculature of the uterus may 
suffer a longitudinal rent. Disease of the muscle, faulty position of the 
uterus, which impedes its propulsion of the fetus in the correct axis, 
favor rupture. The most frequent and serious consequence of rupture 
is peritonitis. Occasionally, when rupture has occurred during preg- 
nancy, the fetus may be enclosed in a sac formed by circumscribing 
peritonitis; the rupture may at the same time heal. Subsequently the 
fetus may be disorganized and discharge through the abdominal wall. 
This is a very unusual termination. 

Laceration of the cervix uteri is a very common accident of labor. 

CIRCULATORY DISTURBANCES 

Hyperemia of the uterus is a physiological condition during men- 
struation, and occurs in all forms of acute inflammation of the organ. 
There is no essential difference between menstrual hyperemia and that 
of pathological conditions. 

Menstruation. — Examination of the mucous membrane during the 
period shows swelling of the membrane, with multiplication of the 
interglandular cells and dilatation of the lymphatic channels. The 
uterine glands are elongated and the cells more or less swollen. Conges- 
tion is always conspicuous, and the superficial epithelial cells are des- 
quamated more or less considerably. In the interval between the 
periods regeneration of the mucous membrane takes place. The term 



776 A TEXT-BOOK OF PATHOLOGY 

dysmenorrhea membranacea is applied to abnormal menstruation in which 
membranous formations are discharged from the uterus (Fig. 375) 
and in which there is severe pain. The membranes consist of intact 
portions of more or less degenerated desquamated cells, with or without 
admixture of fibrin. Cases of. this character are particularly prone to 
occur when chronic inflammations of the mucosa have existed, and the 
affection is then termed endometritis exfoliativa. 

Passive hyperemia of the uterus occurs in conditions of general 
venous stasis, but especially when dislocations of the uterus cause 
pressure upon the venous plexuses. The organ is enlarged, the veins in 
the serous surface are prominent, the mucous membrane is dark red, 
and when the congestion is long continued chronic endometritis may 
result. 

Hemorrhages may occur into the uterine cavity, into the wall of the 
uterus, or into the peritoneum outside the uterus. Hemorrhages during 

menstruation and in labor are physiological 
forms. Pathological increase of menstrual 
hemorrhage is spoken of as menorrhagia, 
which may occur in certain general diseases, 
such as anemia, or in consequence of local 
conditions, notably tumors. Intense con- 
gestion of the organ from cardiac disease or 
from malpositions of the uterus may also lead 
to hemorrhages during the menstrual period. 
Hemorrhages between the menstrual periods 
are spoken of as metrorrhagia. This may be 
caused by general conditions, such as the 
hemorrhagic diseases and infections (small- 
pox, etc.), but it is especially frequent as a 
result of local diseases, of which fibroid tu- 
mors and cancer are the most important. 
There is a normal hemorrhage from the uterus 
after detachment of the placenta at parturition which ceases upon 
uterine contraction, but which may continue in case of imperfect con- 
traction, retained placenta, or diseased uterine vessels. 

Hemorrhages into the substance of the uterus are rare and are gen- 
erally due to traumatism. Apoplexy of the uterus is an interstitial 
hemorrhage due usually to arteriosclerosis with uterine atrophy. 

Hemorrhages into the peritoneal cavities or into the cellular tissues 
in the vicinity of the uterus are more frequent. Of the intraperitoneal 
hemorrhages, the most frequent is accumulation of blood in Douglas' 
pouch {retro-uterine hematocele). The blood in this case may come from 
various sources, such as ruptured ovarian follicles, ruptured tubes in 
tubal pregnancy, hematosalpinx, or rupture of varicose veins in the 
broad ligament. The blood may become absorbed without causing other 
pathological results, or it may set up inflammation and result in ad- 
hesions between the uterus and rectum. Not rarely, perforation with 
discharge of the blood through the rectum or vagina occurs. 




Fig. 375. — Membrane dis- 
charged in membranous dys- 
menorrhea (Penrose). 



DISEASES OF THE REPRODUCTIVE ORGANS 



777 



Hemorrhages into the vesico-uterine pouch and hematomata be- 
tween the layers of the broad ligament are rare. 

INFLAMMATIONS 

Inflammation may affect the mucous membrane of the uterus, 
when the term endometritis is applied; or the wall of the uterus, when 
it is termed metritis. The names perimetritis, indicating inflamma- 
tion of the peritoneal covering of the uterus, and -parametritis, inflam- 
mation of the cellular tissues in the vicinity of the uterus, are unneces- 
sary, as these conditions are simply forms of local peritonitis. For 
purposes of convenience the inflammations of the uterus occurring dur- 
ing the puerperium will be separately considered. Some of the condi- 
tions here described as inflammatory are not positively of such nature, 
though no sharp line of division can be drawn between the inflammatory 
and the hyperplastic forms. 

Acute catarrhal endometritis may result from traumatism, or 
from infection with pyogenic organisms or gonococci. Occasionally 
it occurs as a complication of general infectious diseases, such as typhoid 
fever and cholera. The mucous membrane is swollen and intensely 
hyperemic; very often small hemorrhages are observed. Desquamation 
of the epithelial cells, with mucopurulent secretion, causes considerable 
discharge. In most cases the body of the uterus is affected, but in the 
gonorrheal form the cervical portion is the most frequent seat. Very 
intense forms may occasion necrosis of the epithelial cells and the forma- 
tion of pseudomembranous deposits. This is particularly frequent in the 
infectious diseases. 

Chronic endometritis may be the continuation of acute endometri- 
tis, and is especially apt to occur in persons of reduced vitality, such as 
scrofulous or chlorotic women, or in those in whom the circulation is 
sluggish. The influence of passive congestion has already been referred 
to. Very often the etiology is entirely obscure. 

The mucous membrane in the earlier stages is simply swollen, and 
produces abundant mucopurulent secretion. Later, hyperplastic 
changes occur, the hyperplasia affecting either the uterine glands or 
the interstitial tissue. The terms endometritis glandularis and endo- 
metritis inter stitialis have been applied to distinguish these varieties. 
In the former, microscopical examination shows an abundance of pro- 
liferated glandular acini extending through the depth of the mucous 
membrane (Fig. 376). In the latter the glands are less conspicuous, but 
round-cell infiltration and abundant connective-tissue hyperplasia be- 
tween the glands are conspicuous features (Fig. 377). In some of the 
cases, particularly in those of the glandular form, the process seems more 
closely allied to tumor formation than to inflammation; and it is very 
difficult to draw a sharp line between some forms of adenoma and 
sarcoma of the mucous membrane on the one hand, or chronic inflam- 
mations on the other, in attempting which, one should remember that 
the glandular layer lies immediately upon the muscle, so that acini as 
deep as the muscle-bundles do not necessarily indicate malignancy. 



778 



A TEXT-BOOK OF PATHOLOGY 



The mucous membrane may in the advanced stages be considerably 
swollen and project in a polypoid form (Fig. 378). Later, atrophy may 
take the place of hypertrophy, and in some instances the lining epithelial 
cells lose their cilia and change their character from the typical columnar 




Fig. 376. — Glandular endometritis. 

cells to a distinct squamous type. The small glands of the membrane 
may be obstructed at their mouths and cystic distention may result. 
This is particularly conspicuous in the case of the Nabothian glands of 




Fig. 377. — Interstitial endometritis. 



the cervix, and retention cysts of these glands may reach the size of a 
pea or a small cherry. Occasionally, erosions or slight ulcerations are 
met with in cases of chronic endometritis. 

Chronic endometritis of the cervix is frequently secondary to in- 



DISEASES OF THE REPRODUCTIVE ORGANS 



779 



flammations of the vagina, and may be due to gonorrheal infection or 
other causes. The mucous membrane of the cervical canal is greatly 
thickened, and may project from the os uteri (ectropium). Retention 



TV 



Fig. 378. — Polypoid endometritis (Penrose). 

cysts of the Nabothian glands are sometimes a conspicuous feature, 
and cystic mucous polyps are not unusual. 

The tears and erosions incident to repeated pregnancies, especially 
if any be mechanically delivered, combined with hyperemia from 
uterine malpositions, favor chronic endocervicitis. 

Chronic endometritis may lead to chronic metritis, or by extension 
may occasion tubal disease. Clin- 
ically, it is characterized by more 
or less constant mucopurulent 
discharge. 

Erosions of the uterus are espe- 
cially frequent in the cervix; they 
result from endometritis. The 
mucosa within the cervical canal 
undergoes hyperplastic changes 
and projects from the os uteri in 
a polypoid form. Between the 
papillomatous projections cystic 
formations may develop, and 
these may rupture, leaving ex- 
posed ulcerations. Granulation 
tissue is developed and sometimes 
becomes exuberant in character. 

The term "erosion" is also applied to areas in which the normal squam- 
ous epithelium of the cervix has become converted into cylindrical, or in 
which the cylindrical epithelium of the body of the uterus has extended 
downward to the cervix. Other erosions are due to lacerations of the 
cervix (Fig. 379), and occasionally congenital erosion has been observed. 




Fig. 379. — Left lateral laceration of the cer- 
vix, with erosion (Penrose). 



780 



A TEXT-BOOK OF PATHOLOGY 



Phagedenic ulceration of the cervix has been described as an inde- 
pendent disease. Some of the cases are undoubtedly instances of ulcer- 
ating carcinoma; in other cases ulcerations in this situation have been 
met with in which microscopical examination showed no evidence of 
carcinomatous tissue. 

Acute metritis is rarely met with except during the puerperium, 
but may be the result of acute endometritis. The wall of the uterus 
becomes thickened, soft, and edematous. Occasionally purulent infil- 
tration is observed. 

Chronic metritis frequently occurs in the puerperium as a result 
of retarded involution of the uterus. It may be occasioned by chronic 
congestion of the uterus, or may be secondary to chronic endometritis. 
The uterine wall is infiltrated with round cells, and the connective 
tissues undergo active hyperplasia, which in the later stages leads to 
great thickening and induration. Coincidently, there is usually some 
hypertrophy of the muscular elements themselves. It is by no means 
certain that all of the cases grouped under this term are inflammatory 
in nature. Some are certainly more closely allied with diffuse tumor 
formation. The mucous membrane is usually thickened, and becomes 
secondarily involved if it was not primarily diseased. The peritoneal 
covering may be similarly affected, and chronic perimetritis with adhe- 
sions of the uterus results. 

INFECTIOUS DISEASES 

Puerperal Infections. — This term may be applied to various forms 
of infection occurring during the puerperium, but in the majority of 
instances the streptococcus is the specific organism. 

Etiology. — Two important factors are concerned: (a) Injuries to 
the surface of the uterus, vagina, or vulva; and (b) some form of infec- 
tion. The more or less denuded surface of the uterus offers a ready 
entrance to micro-organisms, as well as an absorptive surface for soluble 
poisons produced by micro-organismal decomposition within the uterus; 
and infection may take place without any further injury than that occa- 
sioned by the normal processes of labor. In most instances, however, 
there is actual injury either of the surface of the uterus, cervix, vagina, 
or vulva, and the micro-organisms or poisons are admitted through 
these wounds. There may be primarily, however, more than a simple 
injury of the mucous surface. In consequence of prolonged pressure 
necrotic lesions terminating in gangrene may first be established, and 
from this secondary infections may take place. In cases in which infec- 
tion occurs without injury to the walls, as well as in cases in which 
injury has been sustained, the pathogenic organisms may first find 
a lodgment and multiply within blood-clots or retained secundines 
within the uterus; and the organisms or their toxic products are sec- 
ondarily admitted to the uterine tissues. 

Puerperal infection is probably in most cases the result of the en- 
trance of micro-organisms from without, and may be traced to want 



DISEASES OF THE REPRODUCTIVE ORGANS 



781 



of cleanliness on the part of the accoucheur or the surroundings. Some- 
times widespread epidemics have been caused by the carelessness of a 
single obstetrician, whose hands perhaps had become infected from oper- 
ating upon or examining cases of erysipelas, general pyemia, or the like. 

Among the micro-organisms, as has already been stated, the Strepto- 
coccus pyogenes is most important. Staphylococci of various sorts, 
bacilli resembling the Bacillus coli communis, the bacillus of tetanus, 
gonococci, and other organisms occasionally infect the puerperal uterus, 
but in these instances the pathological conditions are different from 
those met with in ordinary puerperal infection, which may be con- 
sidered as practically always a streptococcic infection. 

Pathological Anatomy. — In most instances there is primarily a 
lesion upon the mucous surface of either the uterus, the vagina, or the 
vulva. The nature and extent of this depend upon the amount of in- 
jury occasioned during labor. In some instances the lesion is trivial in 
extent, and remains so, though widespread infection results from it. 
In most cases, however, there is a rapidly spreading inflammation of 
the endometrium or mucosa of the vagina, and pseudomembranous de- 
posits are very frequently met with upon the surface. Necrotic and 
gangrenous changes in the mucous membrane are most pronounced in 
cases in which prolonged pressure has been exerted by the head in its 
descent or by instruments. 

The extension of the infection may occur in two ways, either through 
the blood-vessels or through the lymphatic channels; and the local and 
general lesions vary correspondingly. 

In cases in which the infection spreads along the blood-vessels there 
may be primarily septic softening of the thrombi within the uterus 
and purulent phlebitis of the venous channels at the placental site. 
Thrombosis extends from this situation through the veins to the various 
plexuses in the vicinity, and infected emboli are carried through the 
circulation to distant organs, such as the lungs, the kidneys, and the 
spleen. Metastatic abscesses and inflammatory swelling of the affected 
organs result. The kidneys in particular are often the seat of numerous 
punctate or miliary abscesses. 

In the cases in which extension occurs along the lymphatic channels 
the uterus is enlarged, soft, and often pultaceous. Streaks or lines of 
light color may be observed running from the mucous surface toward 
the periphery. These represent the lymphatic vessels filled with puru- 
lent exudate. The walls of the lymphatics may be penetrated, and peri- 
lymphangitic abscesses are thus occasioned. When the process has ex- 
tended to the lymphatics in the outer layers of the uterus, phlegmonous 
inflammation of the subperitoneal tissues (parametritis) results, and 
finally the peritoneum itself may be involved. 

The spleen is enlarged, though less decidedly than in the form in 
which infection occurs through the blood-vessels. 

Extension along the mucous membrane itself may lead to asso- 
ciated disease of the tubes; more frequently the tubes are invaded at 
their abdominal end after peritonitis has developed. 



782 



A TEXT-BOOK OF PATHOLOGY 



Puerperal sepsis is peculiarly virulent and rapid in its course, 
and may occasion widespread changes in all of the tissues of the 

body. 

Tuberculosis of the uterus is 
most frequently met with in the 
mucous membrane of the uterine 
body, and is usually secondary to 
disease of the tubes. Direct infec- 
tion may possibly occur through 
coitus, but is certainly rare. The 
disease occurs in the form of a 
nodular or diffuse infiltration with 
a tendency to rapid ulceration or 
caseous necrosis involving the mu- 
cous membrane and to some extent 
the submucosa. The entire cavity 
of the uterus may be covered with 
caseous and necrotic deposits (Fig. 
380). In the later stages the proc- 
ess may extend deeply, even in- 
volving the muscular layer of the 
organ. The cervix is rarely at- 
tacked. Sometimes miliary tuber- 
cles are found in the uterine mucosa without marked degeneration (Fig. 
381). 




Fig. 380. — Diffuse tuberculosis (ulcera- 
tive and caseous) of the endometrium 
(Kauf mann) . 



.- '--„<!. : . 



* WW- 



mm 





Fig. 381. — Miliary tuberculosis of the endometrium and glandular endometritis (Beyea). 

Syphilis of the cervix uteri may occur in the form of a chancre, a con- 
dyloma, or as tertiary infiltration, but active lesions of the body are rare, 
although it is infected as indicated by syphilitic placentas and fetuses. 



DISEASES OF THE REPRODUCTIVE ORGANS 



783 



ATROPHY AND DEGENERATION 

Puerperal Atrophy. — The uterus suffers a most remarkable atrophy 
following labor. This proceeds very rapidly at first, and then more 
slowly; and under favorable conditions the organ resumes its previous 
condition in the course of a few months. The muscular fibers decrease 
progressively, from their previous hypertrophied condition in which 
they frequently attain a length and diameter three times the normal, 
until, at the end of involution, the usual size and appearances are at- 
tained. Many muscle-fibers undoubtedly are destroyed. The process 
of involution is really one of fatty degeneration. 

Senile Atrophy. — The uterus undergoes progressive atrophy at and 
after the period of the menopause, and finally becomes greatly reduced 
in size. The substance of the organ may undergo a progressive sclerosis, 
or in other instances becomes softer than normal. Catarrhal endo- 
metritis is often associated, and the columnar cells are sometimes con- 
verted into squamous epithelium. 

Fatty degeneration, independent of that which occurs during 
puerperal involution, is a rare condition, but may occur in the course 
of certain infectious diseases, such as typhoid fever, or may result from 
the action of the parenchyma poisons. 

Amyloid infiltration is rare and unimportant. 

HYPERTROPHY AND HYPERPLASIA 

Hypertrophy of the entire uterus may occur in association with 
inflammation or metritis, or may result from chronic congestion of the 
organ. The enlargement in cases usually designated as hypertrophied 
is, for the most part, due to new formed connective tissue. True hyper- 
trophy occurs as a physiological process during pregnancy. In this 
variety the muscle-fibers increase enormously in size, and doubtless also 
multiply their number. The blood-vessels and connective tissues under- 
go corresponding hypertrophy. 

Hypertrophy of the cervix uteri is occasionally met with inde- 
pendent of hypertrophy of the uterus as a whole. It may be caused 
by chronic irritations of the cervix, as in cervical endometritis, or may 
result from obscure causes. Frequently it is met with in prolapse of 
the uterus, and sometimes its elongation simulates prolapse. 

Hyperplasia of the mucous membrane of the uterus has been re- 
ferred to in the discussion of Chronic Endometritis. In some instances 
that are designated as endometritis the pathological process seems to 
be rather of a purely hyperplastic character, and more closely allied to 
tumor formation than to ordinary inflammation. In these cases the 
mucous membrane in all parts of the uterus may be greatly thickened, 
and may suffer more or less papillomatous transformation. Sometimes 
limited portions are affected, and polypoid formations result. 

Polypi of the uterus may be of various sorts. Very commonly 
they present themselves as simple mucous polypi, due to projection of 



784 



A TEXT-BOOK OF PATHOLOGY 



parts of the mucous membrane; in other cases secondary changes, such 
as cavernous dilatation of the blood-vessels or cystic transformation of 
the small glands contained in the polyp, occasion marked variations from 
the original appearances. Myofibromata, sarcomata, and other forms of 
tumors originating in the mucous membrane or just beneath it may 
assume a polypoid appearance. 

TUMORS 

Leiomyoma; Myofibroma; Fibroid. — The tumors of the uterus 
designated by these terms are in nearly all cases composed of smooth 
muscle-fibers and fibrous tissue, and from the pathological standpoint 
the term "myofibroma" is, therefore, most applicable. There are many 
grades of combination in these tumors. Beginning with the soft red, 
illy outlined tumor composed almost entirely of muscle-cells, they pass 
into forms of paling color and increasing consistency to the almost stony 




Fig. 382. — Interstitial fibroid tumor of the uterus: a small submucous fibroid appears in 
the uterine cavity (Penrose) . 

hard fibroid mass, which shows either no muscle-cells or only the fattily 
degenerated remains thereof. They present themselves in the form of 
rounded and usually well-circumscribed masses, from the size of a grape- 
seed to that of tumors weighing 40 or 50 pounds. They are generally 
multiple, and on section have the appearance of concentric or irregular 
lamellae. Microscopically, the tumors are composed of smooth muscle- 
fibers and of fibrous tissue arranged in bundles or layers running in 
various directions. The muscle-fibers are frequently found arranged 
concentrically about small blood-vessels, and in some instances the 
vessels are telangiectatic. 

Secondary changes are very common, the most frequent being 
calcification. This may begin either in the center or at the periphery, 
but more commonly it is diffuse. Edema of the tumor may cause it to 



DISEASES OF THE REPRODUCTIVE ORGANS 



785 



become quite soft, and cystic transformations due to softening or to 
distention of the lymphatic spaces are sometimes observed. Inflam- 
mation may arise and myxomatous or sarcomatous change is known. 

Several varieties have been distinguished, according to the seat 
of the tumors. In some instaces they are embedded in the wall of the 
uterus, when the term interstitial or mural fibroids is applied (Fig. 382). 
In other cases they arise in the uterine walls just beneath the mucous 
membrane, when they are called submucous fibroids, These may gradu- 
ally project into the cavity of the uterus as fibroid polypi. In the third 
group of cases the tumors have a subperitoneal location, and may pro- 
ject from the outer surface of the uterus as knobbed masses (Fig. 383), 
which may become pedunculated. In rare instances they extend be- 
tween the layers of the broad ligament. Fibroid tumors are benign in a 
pathological sense, but occasion serious disturbances either by pressure 




Pig. 383. — Subperitoneal fibroids and an intraligamentous fibroid of the uterus (Penrose). 

or by the metrorrhagia and endometritis to which they frequently give 
rise. Subperitoneal fibroids may become free bodies in the peritoneal 
cavity, and the submucous form is sometimes discharged from the 
uterus after a spurious labor. The so-called adenomyoma and adeno- 
fibroma are tumors including some epithelial structures as nests or 
cystic glands. They are due most likely to a downgrowth of the super- 
ficial epithelial structures, but it has been maintained that they are 
due to remnants of Wolffian body. Some persons view them as results 
of inflammation. They do not grow like simple adenomata nor behave 
like malignant adenomata (Fig. 384). 

Sarcoma of the uterus may arise from the muscular layer or from 
the endometrium. That arising from the myometrium is usually asso- 
ciated with myoma and fibroma. In some cases the sarcomatous ele- 
ments of the tumor are developed in a pre-existing myofibroma. In 

50 



786 



A TEXT-BOOK OF PATHOLOGY 



other cases the sarcoma and fibroma are coincidently formed. These 
tumors differ from typical fibroids in being more rapid in growth, less 
well circumscribed, softer, and more homogeneous in appearance. 
Sometimes they are situated just beneath the endometrium, and be- 
come converted into sarcomatous polypi. 

Sarcoma of the endometrium may occur in a circumscribed or 
papillomatous and in a diffuse form, the latter involving the entire 
mucous membrane of the organ. The papillomatous variety is soft 
and villous and highly vascular. In some cases the structure is that of 




Fig. 384. — Cystic fibre-adenoma of uterus. 



angiosarcoma. In the diffuse form the entire cavity of the uterus may 
be filled with soft villous projections from the mucous membrane. 

A special form of sarcoma has been described as occurring in the 
vaginal portion and cervix. In this the tumor has a grape-like structure, 
and, microscopically, consists of myxomatous tissue with areas of sarco- 
matous character. It occurs in young persons, even in childhood. 

Syncytioma Malignum. — (See p. 238.) 

Adenoma may occur in the form of polypoid outgrowths from the 
mucous membrane, or as a diffuse process not readily distinguishable 
from that commonly designated as endometritis glandularis. Both of 
these forms are benign. 

Malignant adenoma usually arises from the corpus uteri, and pre- 
sents itself as a soft, irregular elevation of the mucous membrane in a 



DISEASES OF THE REPRODUCTIVE ORGANS 787 

localized area, or diffusely involving a large part of the endometrium. It 
tends to spread through the walls of the uterus, invading the myome- 
trium (Fig. 385), and finally penetrating to the peritoneal covering, where 




Fig. 385. — Malignant adenoma, the section is taken from the deeper parts of the tumor, 
and shows the invasion of the myometrium. 

secondary nodules may develop. Histologically, it is characterized by 
the production of atypical, branched, intercommunicating, or cyst-form- 




Fig. 386. — Carcinoma cervicis uteri, showing penetration of nests into muscle. 



ing gland-acini with comparatively little stroma, the latter being of 
soft fibrous character. The tumor is malignant in its tendency to in- 
vade the wall of the uterus and neighboring structures, and it may 



788 



A TEXT-BOOK OF PATHOLOGY 



become converted into actual carcinoma in the later stages. In such 
instances the acini in places show a heaping of epithelial cells and a 
tendency to destruction of the basement-membrane, with proliferation 
of the cells in the stroma. 

Carcinoma is the most frequent of the malignant diseases of the 
uterus, and usually invades the cervical portion; more rarely it arises 
from the corpus uteri. Carcinomata starting on the vaginal surface of 
the cervix are squamous-celled epitheliomata ; those originating in the 
cervical canal and in the corpus uteri are tubular or glandular car- 
cinomata. 

Carcinoma of the portio vaginalis usually begins from the inner surface 
of one of the lips of the os uteri, and causes a firm infiltration of the af- 
fected portion, the disease penetrating into the submucosa and muscularis. 



durated and ulcerating form, cervical epithelioma may present itself 
as a cauliflower-growth — that is, as a destructive or malignant papil- 
loma. In such cases it is likely that the growth often begins as a 
papilloma, causing irregular elevations, and that the penetration into 
the tissue at the base of the growth is a secondary development. In 
the later stages this form, like the preceding, undergoes ulceration. 
Both varieties, but particularly the latter, frequently cause uterine 
hemorrhages. 

Carcinoma of the corpus uteri and of the cervical canal develops 
from the tubular and racemose glands of the mucous membrane. It 
may begin as an adenomatous growth, subsequently becoming trans- 
formed into carcinoma. Macroscopically, the growth presents itself 



Fig. 387. — Diffuse cancer of the endometrium (Pen- 
rose) . 




Subsequently, ulceration 
takes place, and the diseased 
area becomes converted into 
an elevated and irregularly 
ulcerated surface. Exten- 
sion may take place to the 
vaginal walls and to the tis- 
sues surrounding the cervix 
uteri (Fig. 386). Ulceration 
may establish communica- 
tions between the vagina 
and bladder or rectum. Ex- 
tension upward into the su- 
pravaginal portions of the 
cervix and to the corpus 
uteri may occur through the 
lymphatic channels, or by 
direct invasion. Secondary 
involvement of the lymph- 
atic glands of the iliac, lum- 
bar, and inguinal groups is 
frequent. 



Instead of the usual in- 



DISEASES OF THE REPRODUCTIVE ORGANS 789 

as a villous or papillomatous thickening of the mucosa, either localized 
or diffuse (Figs. 387 and 388). In the later stages considerable involve- 
ment of the wall of the uterus occurs, and even perforation may take 




Fig. 388. — Cancer of the body of the uterus: a large, single cancerous nodule in the 
anterior wall has been divided (Penrose). 

place. Microscopically, the usual appearances of glandular cancer or 
adenocarcinoma are discovered (Fig. 389). 




Fig. 389. — Glandular cancer of the cervix uteri. 



Squamous epithelioma is met with in rare instances in the corpus 
uteri, especially in women of advanced years. The explanation of 
this growth is that it arises from epithelium that has undergone a 



790 



A TEXT-BOOK OF PATHOLOGY 



change from the customary columnar to the squamous form, in conse- 
quence of chronic endometritis. 

Cysts. — Small cysts of the wall of the uterus may be associated 
with various forms of tumors, such as myofibromata ; and a form of 
adenocystoma, probably originating from remnants of the Wolffian 
duct, has been described. Dermoid cysts have been occasionally ob- 
served. 

PARASITES 

Echinococcus cysts are sometimes met with, and a few cases of sup- 
posed Cysticercus cellulosce have been described, though the nature of the 
formations was uncertain. 

The Ovaries 

Development and Anatomical Considerations. — The ovary and 
testis are developed from a primary indifferent sexual gland, which is 
indistinguishable in the two sexes. This indifferent gland is formed on 
the ventromesial surface of the Wolffian body by a localized thickening 
of the mesothelial elements. The ovarian stroma is subsequently formed 
by ingrowths of the surrounding mesoderm. The ovary consists of a 
stroma of peculiar spindle-shaped connective-tissue cells. In the central 
or medullary portion the tissue is highly vascular; the peripheral or 
cortical part contains abundant Graafian follicles in which the ova are 
developed. These follicles are formed from primary tubular indentations 
of the cuboidal or columnar epithelium that covers the organ. These 
indentations are the tubes of Pfliiger. After full development of the 
ovary they are wanting, the greater part, by constriction of the deeper 
portions, having formed primordial follicles. The 'paroophoron, a vestigial 
structure, is the part of the ovary at the hilum. It consists of connective 
tissue and blood-vessels with a number of parallel tubes which are rem- 
nants of the Wolffian body. The same tubules surrounded by connective 
tissue extend outward between the layers of the broad ligament, consti- 
tuting the parovarium. Sometimes part of the Wolffian duct remains 
patulous and constitutes the duct of Gartner. This is the homologue 
of the vas deferens. 

CONGENITAL ABNORMALITIES 

Occasional absence of one or both ovaries has been discovered with 
other developmental defects, or independently. Hypoplasia occurs in 
chlorosis, and occasionally in association with other conditions. Some- 
times supernumerary ovaries have been found. The additional ovaries 
may be formed by division or by separation from one of the normal 
glands. 

CHANGES IN POSITION 

More or less extensive dislocations of the ovaries may occur, the 
most notable being that in which one of these organs descends into a 
hernial sac, occupying either the inguinal or crural canal. Dislocations 
resulting from pressure, adhesions, and the like are frequent. 



DISEASES OF THE REPRODUCTIVE ORGANS 



791 



CIRCULATORY DISTURBANCES 

Active hyperemia, or congestion, may be either a physiological or 
pathological condition. The former occurs during the menstrual 
period, the latter in association with inflammation of the neighboring 
structures or in the earlier periods of inflammation of the ovaries them- 
selves. 

Passive congestion is met with in chronic cardiac diseases, and as a 
result of local obstructions to the circulation by tumors, inflamma- 
tory adhesions, torsion of the tube, and uterine displacements. 

Hemorrhage. — Small hemorrhages into the ovarian tissue are very 
frequent. Their occurrence is usually sufficiently accounted for when 
the functional activity of the organ is considered. At each periodical 
ovulation a small follicle ruptures, to discharge the contents containing 
the ovum. Generally there is a slight extravasation of blood at such 
times, which is subsequently absorbed. At the same time that the ex- 
travasation and absorption are taking place the inner lining of the 
follicle proliferates somewhat, and the cells then undergo fatty degenera- 
tion. The whole process gives rise to a yellowish nodular formation, 
termed the corpus luteum. Subsequently this is removed by absorp- 
tion of the blood and by degeneration and absorption of the prolifer- 
ated cells of the lining membrane, and a small scar alone remains. The 
latter, especially when more than usually fibrous, is known as the corpus 
fibrosum. This is commonly a little pigmented, in consequence of the 
pre-existing extravasation of blood. The corpus luteum, which is de- 
veloped from a follicle formed at the time of impregnation (corpus 
luteum of pregnancy), differs somewhat in character. The epithelial 
proliferation is much more active, and the wall of the follicle is intensely 
congested. Rapid involution does not take place, the follicle often per- 
sisting for considerable periods after the termination of pregnancy, and 
acting, according to some writers, as a glandular organ with an internal 
secretion having an inhibitory effect upon further ovulation, but inciting 
activity in the mammae. 

Exceptionally, considerable hemorrhages may take place into the 
follicles, and small hemorrhagic cysts or cysts containing blood-stained 
liquid may be formed. 

INFLAMMATION 

Inflammation of the ovaries, or oophoritis, is generally a secondary 
condition resulting from an extension of inflammation from the neigh- 
boring reflections of the peritoneum, or from extension of infective 
processes along the Fallopian tube. The extension from the neighboring- 
peritoneum, as well as from the uterus, may be direct — that is, along the 
planes of tissue or through the lymphatic or vascular channels. Acute 
oophoritis is not infrequent in various forms of general infection, such as 
typhoid fever, pneumonia, influenza, etc. Primary oophoritis is prob- 
ably very rare. 

The ovary becomes enlarged, and in the earlier stages is more or less 
congested. Later, the tissues become yellowish, either uniformly or in 



792 



A TEXT-BOOK OF PATHOLOGY 



scattered areas. Finally, the process may terminate in necrosis or abscess 
formation. Since such purulent collections either extend or perforate 
into the tube, tubo-ovarian abscesses arise. Such ovarian abscesses 
may reach a considerable size, and break into any of the hollow viscera 
near by or into the peritoneal cavity. In more favorable cases there 
are only small collections of pus, and these may subsequently become 
inspissated. The most satisfactory of all terminations is in complete 
resolution or in induration (chronic oophoritis). The ovary in chronic 
oophoritis may show the changes most upon or near the surface, a con- 
dition which leads to fibrous adhesions to the peritoneum. Cysts in the 
cortex are common, due to prevention of rupture of the Graafian fol- 
licles. The organ in chronic inflammation, except where cysts are 
numerous or large, is small, white, and quite firm. 

Localized inflammations may sometimes occur about the follicles. 
These may terminate in follicular abscesses, which either discharge 
and lead to scar formation or become inspissated. 

INFECTIOUS DISEASES 

Tuberculosis. — Among the infectious diseases, tuberculosis alone is 
of importance. It may arise as a primary disease of the ovaries, but 
much more frequently is secondary to inflammation of the tubes or 
other parts of the genital tract. It may give rise to the formation of 
small or large cheesy masses, showing a tendency to softening with 
formation of tuberculous abscesses. The ovaries may occasionally 
be the seat of miliary tuberculosis. 

TUMORS 

The ovaries are frequent seats of tumors, both benign and malignant. 
By far the largest proportion are cystic. 

Connective=tissue Tumors. — Fibromata may occur as small nodu- 
lar growths, either single or multiple. In some cases the tumors are of 
considerable size. Combinations of fibroma with leiomyoma may also 
be met with; these myofibromata resemble those of the uterus. Occa- 
sionally fibrosarcoma is encountered. Chondroma is a rare form of be- 
nign tumor, usually teratomatous in nature. 

Sarcoma may occur in the form of spindle-celled sarcoma, fibrosar- 
coma, or, more rarely, as round-cell sarcoma. It appears as a rounded 
tumor with more or less pronounced encapsulation. Degenerations, 
such as myxomatous, are not infrequent, and cystic change may be 
occasioned by dilatation of the follicles. In some cases proliferations 
of the walls of the follicles constitute an important part of the growth. 
To such cases the name "adenosarcoma" may be applied. 

The ovary is a favorite seat of mixed tumors, most of which are 
teratomatous and fall into two classes, solid and cystic, of which the 
latter are more common and important. All sorts of combinations 
among the benign and malignant growths, or mixtures of these, have 
been seen. The benign tumors, especially if cystic, are prone to un- 
dergo malignant change. 



DISEASES OF THE REPRODUCTIVE ORGANS 



793 



Cystic Tumors. — Of the cystic conditions of the ovary we must 
distinguish the simple follicular cysts, and the more important myxoid 
or colloid cystomata and dermoid cysts. Of the cystomata, there are 
two varieties — the papillary and the glandular. 

Follicular cysts are developed by distention of the Graafian follicles 
with dropsical liquid. The ovary may be considerably enlarged by 
cystic cavities, lined with epithelium, and containing clear watery liquid 
or, occasionally, blood-tinged contents. Cysts of this character are very 
common in cases of induration of the ovary following oophoritis. One 
form of this follicular cyst formation is so extensive that it seems as 
if all the potential Graafian follicles had attempted to ripen and had 
filled up with clear fluid. This is the "cystic degeneration of the ovary," 
and forms a large cystic mass with little organ tissue remaining. 

Colloid or myxoid cystomata present themselves as tumors of small 
or large size, having a_ tendency to a multilocular cystic character. 
The cavities are filled with a more or less gelatinous or mucoid liquid. 
Sometimes hemorrhage takes place, and the contents are correspondingly 
altered. Two subvarieties may be distinguished : the glandular and the 
papillary. 

Glandular cystomata are distinguished by the constant prolifera- 
tion of the epithelial elements in the form of acini. This occasions a 
multilocular character, new cysts springing from the walls of the original 
cavity or appearing within the substance of the primary tumor. The 
terms adenocystoma and cysto-adenoma are appropriate. The tumor may 
present itself as a large, single, rounded, unilateral or bilateral cyst with 
insignificant projections of small cysts upon the inner lining; while 
in other cases there is found on section a uniform multilocular character. 
Microscopically, the characteristic feature of these tumors is the forma- 
tion of regular gland acini, showing a single layer of epithelial cells, or 
at most a few layers resting upon a basement-membrane, the lining 
showing a tendency to sprout from or sink into the wall, in either case 
to form new cysts. The stroma of the tumor is composed of fibrous 
connective tissue, with some unstriped muscle-fibers. The contents of 
the cysts have the mucoid or colloid character referred to, and chem- 
ically a substance is discovered that is absent from simple follicular 
cysts of the ovary and is less abundant in papillary cystomata. This 
substance is termed "pseudomucin" or "paralbumin," and is somewhat 
related to mucin. Occasionally, when the cysts are old, the contents may 
be quite watery. 

Cystomata soon destroy the ovary, the unaffected ovarian tissue 
being spread out within the wall of the cyst. The tumor is attached 
in the pelvis by a pedicle consisting of the broad ligament and Fallopian 
tube, and often forms secondary inflammatory adhesions to adjacent 
parts. 

Glandular cystomata arise either from embryonal rests (Pfliiger's 
tubes) or from ingrowths of the surface epithelium of the organ. It is 
generally considered unlikely that they arise from Graafian follicles. 

Papillary Cystomata. — Papillary cysts occur in two forms, the one 



794 



A TEXT-BOOK OF PATHOLOGY 



closely resembling glandular cystoma in its general appearance, the 
other presenting itself as a papillomatous condition of the surface of the 
ovary (Fig. 390). In the former, or papillary myxoid cystomata, large 




Fig. 390. — Papillary adenoma of ovary. 

cystic tumors are developed. On section through these there is found a 
papillomatous or cystic proliferation of the lining membrane, but the 
tendency to the formation of secondary cysts is much less pronounced 




Fig. 391. — Double papillomatous cyst of the ovary: the right cyst has ruptured and is 
turned inside out, showing a mass of papillomata; papillomata have penetrated the 
wall of the cyst; the peritoneum has been infected, and a papillomatous growth appears on 
the fundus uteri (Penrose). 

than in the glandular varieties, and the fibrous stroma is less abundant. 
The secondary cysts in this variety may be formed by fusion of the free 
ends of proliferating papillae, or by myxomatous degenerations within 



DISEASES OF THE REPRODUCTIVE ORGANS 



795 



the stroma of the papillae. The liquid of the cysts resembles that of the 
glandular form, but contains less pseudomucin, and is more frequently 
hemorrhagic. On microscopical examination it is found that the inner 
lining of the cyst and the papillary projections consist of stratified 
ciliated epithelium. Calcareous bodies arranged in a concentric fashion 
(psammoma bodies) are frequently met with in the stroma, as well as in 
the epithelium. The same calcareous bodies are occasionally found 
in glandular cystomata. 

The papillomatous ovarian tumors differ from the glandular in 
being almost invariably bilateral (Fig. 391). Their origin has not as 
yet been certainly determined, but it is probable that they originate 
from the paroophoron, a vestigial remnant of the parovarium. Some 
have held that they may originate from the Graafian follicles or from in- 
growths of the surface epithelium. This is assuredly not a frequent origin. 

The surface papillomata of the ovary present themselves as irregu- 
lar masses of a cauliflower appearance. The papillary projections are 
covered with cylindrical epithelium, as in the cystic form. There is no 
essential difference in structure, and it is probable that in many instances 
the superficial forms result from a rupture of the cystic variety and the 
subsequent external proliferation. 

The papillomatous cystomata and the surface papillomata have a 
marked tendency to carcinomatous transformation, and tend to spread 
to the peritoneum, causing metastatic nodules in the vicinity or through- 
out the entire abdomen. 

Both these cysts, especially the former, give rise to the so-called 
"pseudomyxoma peritonei" when they rupture. The latter cyst is more 
malignant than the former, as it can infiltrate through the cyst wall 
and extend by continuity. Frank carcinomatous change is possible 
with metastases in distant organs. 

Dermoid cysts are frequently met with in the ovary. They may 
occur as small nodules or as very large tumors, and are usually uni- 
lateral. The larger ones substitute the ovarian tissue completely; less 
commonly they may be pedunculated, the ovary in part remaining in- 
tact. Combinations with glandular cystomata are not infrequent. 

The dermoid cyst is a smooth-walled sac, the inner surface present- 
ing somewhat irregular projections and having more or less pronounced 
characteristics of epidermal tissue. The cystic contents are a putty-like 
material of grayish color, containing long blonde hairs and teeth, and 
sometimes ill-developed bone. The grayish material consists of fatty 
detritus containing degenerated epithelial cells, and usually abundant 
cholesterin crystals. The wall of the dermoid cyst, though usually in 
the main composed of epidermal structure, may contain elements of the 
three blastodermic layers. The dermoid cyst may occur in childhood 
or even in fetal life, but usually does not present itself until adult years. 

Secondary changes not infrequently occur. Inflammatory condi- 
tions of the walls may occasion abscess. Sometimes the epithelium 
proliferates actively, and the dermoid, in part or as a whole, is converted 
into a carcinoma. 



796 



A TEXT-BOOK OF PATHOLOGY 



Carcinoma of the ovary may be a primary growth of glandular char- 
acter developing from the follicles, or it may be of a mucous or colloid 
variety, when the ovarian tissue becomes converted into a gelatinous 
mass. In the latter case the tumor tends to spread to the adjacent 
peritoneum, and widespread metastasis along this membrane may occur. 

Mention has already been made of the carcinomatous change in 
cystadenomata. When such metamorphosis occurs one finds distinct 
epithelial cell nests besides the proliferating and atypical gland cavities. 
The solid cancers of the ovary are usually of the medullary type, but 
connective tissue may be prominent. 

Secondary tumors of the ovary, usually carcinomatous, are not 
common, yet when they occur frequently attain great size, out of pro- 
portion to what might be expected from the size of the original mass. 
They may be multiple. Metastasis is commonest from the mammae, 
stomach, and rectum, usually by the hematogenic route or through the 
peritoneum. 

CYSTS OF THE PAROVARIUM 

Cysts of the parovarium may be considered in this place on account 
of their clinical resemblance to ovarian cystomata (Fig. 392). They are 
distinguished, however, by their intraligamentous situation, by their 



r 




! 

j 

Fig. 392. — Cyst of the parovarium: there is no distortion of the ovary; the Fallopian tube 

has been much elongated. 

almost invariably unilocular character, and usually by their clearer 
and more serous liquid contents. The ovary is usually uninjured. The 
inner lining consists of ciliated epithelium. 




DISEASES OF THE REPRODUCTIVE ORGANS 



797 



CYSTS OF KOBELT 

These are thin-walled, pedunculated cysts about the size of a pea 
(Fig. 393). They are frequently met with, and are seated at the side 




Fig. 393. — -Fallopian tube, ovary, and parovarium: a, Hydatid of Morgagni; 6, cyst of 
Kobelt's tube; c, Gartner's duct (Penrose). 

of the ovary. The wall is fibrous, the lining membrane composed of 
cubical epithelium, and the contents a clear serous liquid. The cyst 
results from distention of one of Kobelt's tubes in the parovarium. 

The Fallopian Tubes 

Development and Anatomy. — The tubes are formed from the 
upper ends of Midler's ducts. The lower ends of the ducts fuse to form 
the uterus and vagina. Each tube is covered by a peritoneal coat, and 
its walls consist mainly of longitudinal and circular muscle-fibers. The 
mucosa is thrown into well-marked longitudinal plications, which at 
the uterine end are further complicated by secondary elevations. The 
epithelial lining consists of columnar ciliated cells. 

CONGENITAL ABNORMALITIES 

The tubes may be absent or may be defective. Congenital atresia 
is occasionally observed. The tubes may be unusual in length and 
may communicate with the uterus in abnormal situations. 

CHANGES OF POSITION 

In dislocations of the ovaries the tubes are correspondingly dis- 
located. Independent of displacements of the ovary, the tubes may be 
distorted or pulled out of their usual position by inflammatory adhesions, 
and may thus be bent at sharp angles or bound down in various mal- 
positions. 



798 



A TEXT-BOOK OF PATHOLOGY 



STENOSIS 

Congenital stenosis of the tubes, or complete closure of the lumen, 
may affect the entire length of the tube or a limited portion, princi- 
pally near the middle. Acquired stenosis may result from pre-existing 
disease of the tube itself, or from adhesions secondary to localized 
peritonitis. The most frequent situation in these instances is the ab- 
dominal or fimbriated end. A narrowing of the lumen of the tube may 
be occasioned by angulation or by dislocations. 



DILATATION 

Dilatation on the proximal side of obstructions or stenosis is fre- 
quent. The dilatation is more marked when inflammatory conditions 
of the mucous membrane are present. The abdominal end of the tube 
may enlarge so as to form a cyst of considerable size, filled with serous 
or seromucous liquid, when the middle portion is stenotic. When the 
lower end is obstructed the entire tube becomes dilated, and it fre- 
quently shows a tortuous and irregularly pouched condition, due to its 
attachments to the broad ligament. In such instances the mucous 
membrane is pushed inward at the bends, and projects prominently 
into the lumen of the tube. Secondary changes of the epithelial lining 
are not unusual in consequence of the irritation of the retained secre- 
tions. The normal epithelium may be wholly lost and the lining may 
consist of squamous epithelial cells. Purely inflammatory dilatations 
will be referred to below. 

CIRCULATORY DISTURBANCES 

Active hyperemia of the mucous membrane may be a part of acute 
inflammation of the tubes, and is very frequently found at the fim- 
briated extremity in association with peritonitis. The mucous mem- 
brane is swollen and bright red in color. There may be excess of mucous 
secretion. 

Passive hyperemia occurs in conditions in which the general venous 
circulation in the abdomen is impeded. 

Hemorrhages into the tubes may occur physiologically during the 
menstrual period, and sometimes considerable amounts of blood are 
found under these circumstances. Small hemorrhages into the mucous 
membrane may occur in association with inflammations of the tubes 
and in the course of some of the infectious diseases. 

Hematoma of the tube, or the collection of blood in the tube, results 
from stenosis of the uterine end with accumulation of the menstrual 
discharges in the outer portions. The blood may remain in a more or 
less natural condition for a long time, or may undergo secondary changes. 
Sometimes it discharges through the abdominal end of the tube into 
the peritoneal cavity and leads to retro-uterine hematocele. 



DISEASES OF THE REPRODUCTIVE ORGANS 



799 



INFLAMMATIONS 

Inflammation of the tubes, or salpingitis, may be acute or chronic. 

Acute salpingitis presents itself in several forms, such as an acute 
catarrhal and a suppurative form. In most cases the inflammation 
results from the entrance of irritants from the uterus, and the tubal 
disease is secondary, therefore, to endometritis or to other disease of the 
uterus. Among the micro-organisms discovered, streptococci, staphy- 
lococci, the Diplococcus pneumonia, and the Bacillus coli communis may 




Fig. 394. — Acute septic salpingitis: section about the middle of the tube (Beyea). 

be mentioned, but the gonococcus is by all means the most frequent 
in the non-puerperal cases. The infective organisms may extend di- 
rectly along the mucous membrane or, more rarely, may reach the 
tubes through the lymphatics. In rare instances salpingitis may be 
secondary to local peritonitis. 

Pathological Anatomy. — In acute catarrhal salpingitis the mucous 



800 



A TEXT-BOOK OF PATHOLOGY 



membrane is swollen, hyperemic, infiltrated with round cells, and cov- 
ered with more or less abundant mucous secretion, which may distend 
the tube considerably. In the later stages the secretion is apt to become 
mucopurulent. Interstitial inflammation with thickening of all of the 
layers of the tube wall, is frequently a secondary result. In acute sup- 
purative salpingitis the walls of the tube are infiltrated with round 
cells (Fig. 394), the mucous surface discharges abundant pus, and the 
tubes may become distended with this exudate if the abdominal and 
uterine ends are closed by the inflammatory process. The mucous 
membrane in these cases is intensely inflamed and often slightly ulcer- 
ated upon the surface. Sometimes the distention is so great that the 
tubes are converted into pus-sacs the size of an egg or a small lemon. 
In case of acute suppurative or necrotic salpingitis secondary to puer- 
peral sepsis the mucous membrane may be covered with a necrotic 
membrane; the term diphtheritic salpingitis has sometimes been applied 
to such a condition. 

The exudates within the tube may remain for a long time without 
change, or may undergo gradual inspissation, and sometimes even 



Tig. 395. — Chronic salpingitis: both Fallopian tubes are closed and adherent (Penrose). 

calcification occurs. When ulcers of the mucous membranes have 
formed, rupture of the tube and consecutive peritonitis may occur, 
especially during straining efforts, as in labor. Acute local or general 
peritonitis more frequently results from discharge of infective matter 
from the abdominal end of the tube. Localized peritonitis is very 
common in acute cases, but the tube rarely ruptures under ordinary 
circumstances. It seems very distensible and localizing adhesions soon 
form, as in the case of any peritoneal congestion. 

Microscopically, in all forms of salpingitis extensive round-cell in- 
filtration is observed in all of the layers of the tubes. Plasma cells are 
especially prominent. 




DISEASES OF THE REPRODUCTIVE ORGANS 



801 



Chronic salpingitis, as a rule, results from the continuation of an 
acute form. The wall of the tube becomes thickened and the muscular 
layer is often hyperplastic. Proliferative changes in the mucous mem- 
brane are not unusual and may lead to actual polypoid outgrowths. 
Occasionally small follicular formations are seen in the mucosa, but 
ulcerations of the mucous membrane are infrequent. When the in- 
flammation extends to the serous coat, inflammatory adhesions are fre- 
quently formed (Fig. 395), and may bind the tube firmly to adjacent 
parts and occasion great congestion or distortion. Very often the ab- 
dominal end of the tube becomes occluded by inflammatory adhesions 
or by inversion and agglutination of the fimbriae. At the same time the 
swelling of the mucosa obstructs the uterine end, and in consequence the 
tube becomes a closed pouch which fills with pus (pyosalpinx) , sero- 
purulent liquid (hydrosalpinx, Fig. 396), or hemorrhagic fluid (hemato- 




Fig. 396. — Hydrosalpinx, showing complete inversion of the fimbriae (Penrose). 

salpinx). Intercurrent acute salpingitis frequently takes place in cases 
of chronic tubal disease. 

INFECTIOUS DISEASES 

Tuberculosis of the tubes may be either primary or secondary, and 
is probably much more frequent than has been supposed. Secondary 
tuberculosis may occur in the miliary form in association with tubercu- 
losis of the peritoneum, other parts of the genitalia, or with general 
tuberculosis. In other cases secondary tuberculosis leads to caseous 
and fibrous changes in the walls of the tubes. The latter become greatly 
thickened, and, microscopically, there is found a diffuse cellular infiltra- 
tion with scattered giant cells and here and there definite tubercles. 
The fibrous changes progress more slowly, and may eventually become 
the conspicuous feature. Primary tuberculous salpingitis is similar in 
its appearance to the form just described. The infection may occur 
through entrance of the organisms at the uterine end of the tube, and 
certain observations would indicate that pre-existing gonorrheal sal- 
pingitis predisposes to secondary tuberculous infection. There are 

51 



802 



A TEXT-BOOK OF PATHOLOGY 



usually inflammatory adhesions of the tubes to the neighboring organs, 
and particularly to the ovary, and secondary miliary tuberculosis of the 
peritoneum is frequently observed (Fig. 397). The lumen of the tube 
is filled with purulent liquid, and sometimes certain portions, particu- 
larly the abdominal end, may be greatly distended, forming cysts con- 
taining puriform liquid. 




Fig. 397. — Tuberculosis of the Fallopian tubes. The disease has extended to the perito- 
neum, which is covered with tubercles (Penrose). 

Syphilis has been observed in the form of gummata, and also in the 
form of diffuse sclerosis, in cases of congenital origin. 

TUMORS 

Fibromata and fibromyomata are met with in the external walls of 
the tubes as nodular masses. They frequently undergo secondary calci- 
fication. Lipoma occurs in the external coat lying between the layers 
of the broad ligament. 

Papillomatous elevations of the mucous membrane are quite fre- 
quent, and in some cases a transformation of papilloma to carcinoma 
takes place. Probably most instances of primary carcinoma of the 
Fallopian tubes have this origin. Secondary carcinoma may result from 
extension of uterine cancer. 

Sarcoma occurs in various forms, and syncytioma malignum may 
affect the tubes after tubal pregnancy. 

Cysts of the tubes are usually the result of localized distentions of 
the lumen in consequence of obstructions. Small cystic formations of 
obscure origin are sometimes found in the peritoneal covering of the 
tubes and along the attachment of the broad ligament. Their contents 
may be colloid or serous. 

The hydatids of Morgagni are small cystic formations about the size 
of a pea, hanging by a long pedicle at the fimbriated end of the tube. 
They are probably the result of distention of the closed end of Muller's 
canal. 

Tubo-ovarian cysts are formed by distention of the abdominal end 



DISEASES OF THE REPRODUCTIVE ORGANS 



803 



of the tubes when the fimbriated extremities are attached to the ovary, 
or in other cases may be the result of rupture of follicular cysts of the 
ovaries themselves into the abdominal end of the tubes. 

PARAMETRIUM 

The tissues below the tubes and ovaries at the sides of the uterus 
are known as the parametrium, a highly vascular area containing the 
draining elements of the pelvis. It is of great pathological importance 
in the various inflammatory lesions emanating from the lower uterine 
segment. As infection spreads from this region the parametrium re- 
acts promptly with serous, then cellular, exudate, and an acute inflam- 
matory mass arises. While it is, in a sense, a local peritonitis, the pos- 
sibility of infective thrombosis of the large veins render spread of in- 
fection easy, and the chronic adhesions remaining after recovery lead to 
uterine displacements and fixative adhesions. Abscesses may spread to 
Douglas' pouch. Hemorrhages from the large vessels in the parame- 
trium may spread into this pouch or between the layers of the broad 
ligament. 

EXTRA-UTERINE PREGNANCY 

Etiology. — Any obstruction to the downward migration of the ovum 
may lead to its retention and development in abnormal situations. The 
actual case is usually difficult to determine. Impregnation possibly fre- 
quently takes place in the Fallopian tube; but unless some obstruction 
arrests the passage of the ovum into the uterus, normal uterine gestation 
takes place. Swelling or rapid decidua formation of the mucosa of the 
tubes may be one of the causes, and chronic salpingitis, by causing de- 
struction of the cilia of the epithelial cells and thickening and adhesions 
of the walls of the tubes, acts in a similar manner. Any other form of 
obstruction, as by tumors or external compression, may be included 
among the etiological factors; a condition of some importance in the 
causation of ectopic pregnancy is the presence of diverticula of the 
tube near the uterus where an impregnated ovum may lodge. 

Varieties and Pathological Anatomy. — All cases of extra-uterine 
pregnancy are probably in the beginning tubal pregnancies. This 
condition may occur in any part of the tube. It is rarely found at the 
uterine end, but may occur there in that part of the tube which is 
embedded in the wall of the uterus. The term interstitial pregnancy is 
applied to this form. 

Tubal Pregnancy. — The changes which occur in the tube are analo- 
gous to those met with in the uterus. The same forms of membranes 
and deciduse are developed, and a placenta develops as in the uterus. 
The muscularis of the tube may hypertrophy somewhat, but in the end 
the increasing size of the contained ovum leads to thinning and stretch- 
ing of the walls of the tube. It is an interesting fact that the mucous 
membrane of the uterus forms a decidua of more or less complete de- 
velopment in cases of extra-uterine pregnancy (Fig. 398). 

Among the terminations of tubal pregnancy are the following: 



804 



A TEXT-BOOK OF PATHOLOGY 



1. The tube may rupture into the broad ligament, into the perito- 
neal cavity, or, in cases of interstitial pregnancy, into the uterus. As a 
result of these accidents hematoma of the broad ligament, hematocele, 
and local or general peritonitis may occur, or sudden death may take 
place as a direct result of the hemorrhage. Sudden death from collapse 
is more frequently due to this cause than has generally been supposed. 

2. The ovum may be destroyed in the tube and the gestation cease. 
In this case the fetus subsequently undergoes various changes. More 
or less degeneration usually occurs, and shapeless masses or adipocere 
may result. In other cases calcification of the remnants of the disor- 
ganized fetus leads to the formation of a lithopedion. This may take 
place within the tube, or after rupture of the tube and enclosure of the 
fetus in a sac formed by circumscribing peritonitis. 

3. Premature discharge of the ovum (tubal abortion) may occur, 
and the gestation may terminate without serious results. In other 
cases, however, it leads to a discharge of the blood through the unclosed 



.CHOR.ro/Nlt3 V/1LLI 




Fig. 398. — Tubal pregnancy, removed before rupture. The opening that has been cut in 
the tube shows the chorionic villi (Penrose). 

abdominal ostium of the tube into the peritoneal cavity; and hematocele, 
peritonitis, or sudden death from hemorrhage may occur. 

4. In very exceptional cases tubal pregnancy goes on to full term 
without rupture of the tube. Spurious labor may then come on, the 
fetus, as a rule, perishing. The liquor amnii is absorbed, and degenera- 
tive changes leading to mummification, or the formation of adipocere or 
of a lithopedion, take place. The mummified fetus may remain for 
many years. Very rarely after spurious labor the fetus is discharged into 
the peritoneal cavity, and may be delivered through the rectum or in 
other ways. 



DISEASES OF THE REPRODUCTIVE ORGANS 



805 



Abdominal Pregnancy. — This term is given to cases in which the 
tube has ruptured and the ovum, enclosed in its membranes, escapes 
into some part of the abdominal cavity, where it remains free or sur- 
rounded by adhesions the result of peritonitis. The placenta, as a rule, 
remains in the tube; but it may also establish secondary attachments to 
parts of the peritoneum. Primary abdominal pregnancy — that is, im- 
pregnation and gestation in the abdominal cavity — does not seem ever 
to occur. 

The Vagina 
prolapse of the vaginal walls 

Prolapse of the anterior or posterior wall of the vagina may be due 
to abnormal relaxation of the tissues, or it may be secondary to pro- 
lapse of the uterus and similar conditions that press the vaginal walls 
downward. Xot infrequently the posterior wall of the bladder is dragged 
downward with the anterior wall of the vagina, and vaginal cystocele 
results. Similarly, the anterior wall of the rectum may be carried down- 
ward with the posterior wall of the vagina; this is termed vaginal recto- 
cele. 

STENOSIS OF THE VAGINA 

Congenital stenosis is rare. More frequently the lumen of the 
vagina is narrowed by contraction of cicatricial tissues formed in in- 
flammatory diseases of the walls, or by adhesion of the opposite surfaces 
following ulcerations. Complete occlusion may occur in the latter form 
of cases, especially in old women. Atresia leads to obstruction of the 
discharges from above, and when menstruation is due causes collection 
of blood in the vagina (hematocol pos) and in the uterus (hematometra). 

WOUNDS AND FISTULA 

Injuries to the vaginal walls may be caused by the insertion of sharp 
bodies or instruments, or by coitus. Much more frequently injuries 
are due to stretching or pressure during labor. Superficial lacerations 
caused by overdistention are frequent, but more extensive injuries may 
be caused by prolonged pressure of the infant's head or by instruments 
used in delivery. In such cases infection and phlegmonous inflamma- 
tion are prone to occur, and vesicovaginal, urethrovaginal, or recto- 
vaginal fistulae are sometimes the result. The urine or feces may be 
discharged through the vagina, and often cause secondary inflammations 
of the entire vaginal mucosa. 

Similar fistulae may be due to ulcerative processes of other kinds, 
to necrosis of carcinomata of the vagina, or to diseases of the bladder or 
rectum. 



806 



A TEXT-BOOK OF PATHOLOGY 



CIRCULATORY DISTURBANCES 

Active hyperemia occurs in the early stages of inflammation. The 
mucous membrane is light red in color and a little swollen. 

Passive hyperemia is frequent in pregnancy, and occurs in conse- 
quence of pressure due to other causes, such as uterine tumors and the 
like. The mucosa becomes swollen and edematous, and may be moist 
from increased secretions. 

Hemorrhages into the vaginal walls are most frequently due to 
traumatism. Inflammation and ulceration may result from the hemor- 
rhagic extravasation. 

INFLAMMATIONS 

Acute Catarrhal Inflammation, Vaginitis, or Colpitis. — This 

condition is frequently due to gonorrheal infection, but may result from 
other causes, such as mechanical and chemical irritants, or in young 
girls from the invasion of the Oxyuris vermicularis from the rectum. 
The mucous membrane is usually deeply congested, and the surface is 
covered with mucopurulent exudate. In gonorrheal cases the cervix 
uteri and urethra are, as a rule, coincidently affected. 

Exfoliative Vaginitis. — In rare cases of intense catarrhal vaginitis, 
in which the deeper layers of the mucosa are principally involved, 
membranous formations, consisting of parts of the superficial epithelial 
layers, may be discharged. 

Pseudomembranous vaginitis may occur in asociation with various 
infectious diseases, such as pneumonia, pyemia, cholera, etc.; but it is 
more frequently the result of pressure-necrosis and infection occurring 
during labor, and is one of the lesions of puerperal sepsis. The surface 
of the vagina is more or less extensively covered with a dirty and ex- 
foliating pseudomembrane. After discharge of the latter ulcerations 
are often formed. Extensive necrosis of the vaginal walls may occasion 
great destruction, and in some instances phlegmonous inflammations of 
the perivaginal tissues may cause separation of the mucosa. 

Other forms of vaginitis are erysipeloid, aphthous, and emphysema- 
tous. They are not peculiar in manifestation, but show the usual 
characters of these infections. The identity of the last has been ques- 
tioned. It is supposedly due to an anaerobic organism and is common 
after labor. 

Chronic catarrhal vaginitis may be the continuation of an acute 
inflammation, or may occur in a gradual manner in women reduced 
in vitality. The mucosa usually presents appearances somewhat like 
those of acute cases, though the congestion is less marked. Abundant 
mucopurulent or mucous discharge (leukorrhea) may be present. 
Erosions of superficial epithelium and enlargements of the lymphoid 
follicles are sometimes observed. In long-standing cases the surfaces may 
be smooth and the entire mucosa somewhat indurated (senile vaginitis) . 

Kraurosis vulvas is a hyperplastic condition of the deep connect- 
ive tissue which causes atrophy of the mucosa and submucosa of the 



DISEASES OF THE REPRODUCTIVE ORGANS 



807 



vagina, labiae, and adjacent parts of the vulva. The mucosa of the 
affected areas is dry, glistening and hard, often fissured, and contrac- 
tions of the vaginal outlet are common. The color of the surface is 
grayish or dark red. The etiology is obscure. 

Elephantiasis of the labia? or clitoris may be congenital, or may 
result from local inflammatory conditions or obstructions of the lymph- 
channels. The affected parts are sometimes enormously enlarged. 
The surface is smooth or nodular and is gelatinous or hard in consistency. 
As elsewhere, the histology is that of a fibrous overgrowth with lymph- 
ectasia. 

INFECTIOUS DISEASES 

Tuberculosis may occur in the form of ulcers associated with uterine 
tuberculosis, or in the form of lupus from extension of the latter from 
the vulva. 

Syphilis. — Chancres, mucous patches, and simple inflammation may 
occur in any part of the vagina, and circumscribed (gummatous) or 
diffuse infiltrations have been described. 

TUMORS 

Fibroma and myofibroma may arise in the muscular layer of the 
vaginal wall, and may project as nodular masses or assume a polypoid 
form. 

Sarcoma may occur as a circumscribed mass, but more commonly 
as diffuse infiltration or grape-like masses, which tend to ulcerate. 

Papillomata are not infrequent, in the form of small warts or as 
considerably elevated condylomata. 

Carcinoma of the vagina is most frequently secondary to cervical 
cancer. Similarly, it may follow cancer of the vulva. Primary car- 
cinoma of the vagina is rare. It occurs in the form of a circumscribed 
villous projection. 

Cysts of the vaginal walls vary in size and number. Frequently 
they are multiple, and the size ranges from scarcely discoverable cavities 
to those the size of an egg. The contents are usually serous and color- 
less, or, less frequently, of brownish color. In some instances a flat epi- 
thelial lining has been discovered. The origin of these cysts is probably 
variable. Some seem to arise from remnants of the lower end of the 
Wolffian duct; others are probably lymphangiectatic. The multiple 
small cysts sometimes occurring in pregnancy are due to follicular 
distentions, or to small hemorrhages with subsequent cystic change. 

The Vulva 

The most common anomalies of the vaginal entrance take the form 
of hypertrophy, particularly of the clitoris, but also of the labia, of 
hypoplasia combined with imperfect development higher in the geni- 
talia, of reduplication or fusion of the labia, and of imperforate hymen, 



808 



A TEXT-BOOK OF PATHOLOGY 



or one with several openings. Hernia may occur into a patent canal 
of Nuck in the labia majora. 

WOUNDS 

Injuries of the vulva frequently occur during labor. Laceration 
of the fourchette is very common, and in a considerable proportion of 
cases more extensive tears extending into the perineal body, and some- 
times through this into the rectum, are observed. Prolonged pressure 
and contusion during labor may occasion hemorrhages into the tissues 
of the vulva. 

CIRCULATORY DISTURBANCES 

Active hyperemia is met with in acute inflammations. 

Passive hyperemia and edema occur in conditions in which 
there is general venous stasis, as in cardiac or pulmonary disease. They 
are also met with in pregnancy. The vulva is dark red in color, some- 
times cyanotic; the subcutaneous and submucous tissues become edem- 
atous, and in consequence the labia majora may swell enormously. 

Hematoma of the vulva is caused by compression and contusion 
of the vulva during parturition, or less frequently at other times. 
Varicosity of the veins is a predisposing cause of importance. Con- 
siderable masses of blood ("thrombi") accumulate in the submucous 
tissues of the vulva and vagina. These may be subsequently absorbed, 
or they may discharge through the skin in consequence of superficial 
ulcerations and ruptures. Infection of the thrombus may cause abscess 
of the labia or other affected parts. 

INFLAMMATION 

Acute catarrhal inflammation results from the same causes as 
occasion acute vaginitis. The pathological appearances are, in general, 
the same, though edematous swelling is likely to be more marked. 
Distention of the glands of Bartholin and secondary abscess-formation 
in these glands are common conditions in gonorrheal vulvitis. Vulvitis 
may be of erysipelatous form, upon which gangrene may supervene. 
Noma has been observed on the external female genitalia. 

Epidemic vulvovaginitis of children, in all probability due to the 
gonococcus, appears frequently in hospitals and other institutions. 
The origin and method of spread are often obscure, and the disease is 
very difficult to eradicate. The symptoms and signs may intermit, 
but in their absence the person remains infective. 

Chronic inflammation sometimes follows acute vulvitis. Con- 
siderable hyperplasia of the mucosa is sometimes the result. Erosions 
and ulcerations are less frequent. 

Phlegmonous inflammation, or abscess, of the submucous tissue 
of the labia majora sometimes results from extension of a similar proc- 
ess in the adjacent parts, or may be the direct result of injuries and 
hematoma, with secondary infection. 



DISEASES OF THE REPRODUCTIVE ORGANS 



809 



INFECTIOUS DISEASES 

Diphtheria sometimes attacks the vulva, especially in puerperal 
women. The pathological conditions are similar to those observed in 
other mucous membranes. 

Tuberculosis may occur in the form of lupus. The lesions are 
irregular ulcers with elevated edges and more or less necrotic bases. 

Syphilis. — Chancres and mucous patches are met with on the sides 
of the labia and elsewhere. Condyloma acuminatum, or venereal wart, 
is frequently seen upon the vulvar surfaces. Histological study shows it 
to be a hypertrophy of the dermal papillae with hyperplasia of all layers 
of the epiderm. 

Chancroids occur in the same situations as chancres. Very often 
opposite sides of the vulva are involved by attrition. 

Gangrene of the vulva may be the consequence of severe contusions 
or inflammations occurring in the course of various infectious diseases. 

TUMORS 

Fibroma, fibromyxoma, and myofibroma are occasionally met 
with as nodular tumors or polyps arising from the labia majora. Lipoma 
and sarcoma may present a similar macroscopical appearance. All 
of these growths are rare. 

Elephantiasis vulvae is a not infrequent affection, especially in 
eastern and tropical countries. It may be due to congenital dilatations 
of the lymphatic channels, or to lymphangiomatous tumor-growths. 
More frequently elephantiasis is caused by filariee and inflammatory 
conditions that occasion obstruction to the flow of the lymph. In some 
instances the etiology is very obscure. 

Pathologically, elephantiasis consists of a thickening of the subcu- 
taneous connective tissue, with more or less involvement of the skin as 
well. The disease may begin in the clitoris, or in one or other of the 
labia, and may be confined to the part primarily affected, or may extend 
to other parts. The affected portions are tough and edematous; the 
skin is tightly bound to the subcutaneous tissue. The surface may show 
dermatitis, but in some cases is smooth. Superficial ulcers may occur, 
and sometimes the dilated lymph-channels communicate with the sur- 
face, discharging lymph (lymphorrhea). 

Papillomatous tumors are not infrequent in syphilitic women 
in the form of elevated condylomata. A somewhat analogous condi- 
tion of obscure etiology is that termed caruncle. It presents itself 
as a papillomatous and highly vascular elevation at the meatus of the 
urethra. 

Adenoma arising from the glands of Bartholin has been described. 

Carcinoma is uncommon. It most frequently arises from the 
clitoris, but may affect any portion. Glandular cancer may begin in 
Bartholin's glands. 

Cysts are quite frequent. Small retention-cysts, containing pul- 



810 



A TEXT-BOOK OF PATHOLOGY 



taceous (atheromatous) matter, are sometimes met with in the labia 
majora, and in the great majority of cases are retention-cysts of the 
glands of Bartholin. Larger cysts, containing serous or somewhat blood- 
stained liquid, may result from hematomata, or may be lymphangio- 
matous in origin. Hydrocele of the canal of Nuck has the superficial 
appearances of a cyst of the labia. 

The DEcrouA, Placenta, and Fetal Membranes 

Anatomical Considerations. — The fetus is enclosed within a deli- 
cate fibrous membrane, the amnion, and this is covered with a second 
membrane, the chorion. After the deposit of the ovum in the uterus 
the mucous membrane of the latter undergoes a form of hyperplasia, in 
which the uterine glands and the blood-vessels take part conspicuously, 
and thus the organ becomes lined with a thickened mucosa. The latter 
is termed the decidua vera. A reflection from this covers the fetus en- 
closed in its membranes, the reflection being known as the decidua 
reflexa. At about the fifth month of development the decidua reflexa 
and the decidua vera unite and fuse. The portion of the decidua vera at 
which the placenta is subsequently located is termed the decidua sero- 
tina. In this portion the vascular system is particularly marked, and is 
composed of large venous sinuses with thin walls. The fetal chorion 
carries on its outer surface numerous small projections, or villi. In the 
region of the decidua serotina these villi undergo marked hyperplasia 
and bury themselves between the venous sinuses of the decidua. At 
the junction of the villi and the decidua two layers of cells are developed. 
The first, 'immediately covering the villi, consists of cubical epithelial 
cells (Langhan's cells). Outside of these, and uniting the villi with the 
maternal tissue, is a layer of clear protoplasmic material containing 
large nuclei. This has the appearance of nucleated protoplasm, rather 
than that of collections of cells of definite outline. This protoplasmic 
layer, syncytium, is probably, like Langhans' cells, derived from the 
covering of the chorionic villi, though some authorities contend that it is 
maternal in origin. 

ABNORMALITIES OF DEVELOPMENT 

The Placenta. — Abnormal smallness of the placenta, or hypoplasia, 
and abnormal largeness are occasionally observed. More frequently 
an adventitious placenta {placenta succenturiata) may be attached to the 
main placenta or may lie near it. Abnormal location of the placenta 
at or near the neck of the uterus {placenta pravia) is an important condi- 
tion, from its liability to cause hemorrhage and miscarriage. 

The Umbilical Cord. — Occasionally the cord is divided near its 
placental end into two or more branches. The placenta may be corre- 
spondingly divided or single. The attachment to the placenta may be 
marginal instead of central, and sometimes the blood-vessels spread out 
into a broad marginal attachment, with absence of their gelatinous 
covering. The latter is termed velamentous insertion. 



DISEASES OF THE REPRODUCTIVE ORGANS 



811 



Abnormalities of the blood-vessels, such as branching, a single 
artery, two veins, etc., are unimportant. 

Twists and knots of the cord are frequent, and may strangulate 
the cord and stop the circulation, causing death of the fetus. 

Thickening of the intima of the umbilical vein and of the adven- 
titia of the arteries is probably syphilitic in nature. 

CIRCULATORY DISTURBANCES 

Hydrorrhoea gravidarum is a condition in which abundant serous 
or somewhat turbid liquid is secreted from the deciduee. The condition 
occurs in women suffering from general anemia, but is probably due to 
local conditions within the uterus. Abortion or miscarriage is not 
unusual. 

Hemorrhages from the decidua or into the decidua and placenta 
are not infrequent. Hemorrhages from the surface may be due to pre- 
ceding decidual disease, or may be obscure in origin. Large hemor- 
rhages may cause rapid discharge of the uterine contents. In cases of 
that abnormal position of the placenta called placenta prsevia hemor- 
rhages are frequent. 

Fleshy moles or polypi are the terms used to designate formations in 
the deciduse and placenta resulting from gradual hemorrhage and de- 
struction of the ovum. The hemorrhage takes place in the decidua, and 
then extends between the chorionic villi into the fetal membranes, which 
may be more or less extensively torn apart. Irregular masses of clotted 
blood attached to the placental site and to the chorion are discovered. 
The amniotic cavity contains viscid fluid and the ovum is more or less 
completely disorganized. Sometimes no recognizable remnants can be 
found. The moles may be retained a long time and may undergo 
secondary calcareous infiltration. Usually they are soon discharged. 

Placental Infarcts. — This term is applied to light-colored, more or 
less indurated areas met with in the placenta, decidua?, and sometimes 
in the chorion. The nature of these formations is still somewhat un- 
certain. They are composed of fibrin of reticulated or granular char- 
acter, with occasional areas of softening and hemorrhagic accumula- 
tions, and are not rarely surrounded by a zone of cellular infiltration. 
Some of these "white infarcts" may be only an exaggeration of the 
normal coagulation necrosis occurring toward the end of pregnancy. 
Some are surely due to hemorrhages. When they are extensive it is very 
probable that they represent results of disturbances of circulation 
caused by thickening of the walls of the blood-vessels. 

INFLAMMATION 

Inflammations of the placenta (placentitis), of the chorion villi, 
or of the decidua (endometritis decidualis) may occur in association with 
preceding diseases of the uterus, and especially in cases of syphilis of 
the mother or fetus. The inflammation takes the form of cellular in- 



812 



A TEXT-BOOK OF PATHOLOGY 



filtration and induration. This may begin in the decidua and extend to 
the placenta, and may be of a diffuse or circumscribed character. The 
villi of the placenta may be greatly compressed by the inflammatory 
tissue, and may suffer fatty degeneration and atrophy. In other cases 
the inflammatory changes are most pronounced in the walls of the 
blood-vessels and around the vessels of the chorion and umbilical cord. 
Nodular thickening or diffuse induration results, the latter especially in 
cases in which coincident involvement of the chorionic villi has occurred. 

Diffuse hyperplasia of the decidua is sometimes described as endo- 
metritis decidualis. The inflammatory nature of such cases, however, 
is uncertain. 

INFECTIOUS DISEASES 

Tuberculosis of the placenta was suspected as a possible condition 
long before positive demonstrations were made. In recent years, 
however, a number of undoubted cases have been described. Macro- 
scopically, there may be but little change in the appearance of the 
affected parts. 

Small tubercles, containing giant cells and tubercle bacilli, first 
appear in the decidua serotina, and later invade the placental and 
chorionic tissues between the villi. The epithelial covering of the villi 
undergoes hyperplasia, forming collections of large cells. Warthin 
says that the decidual cells do not form tubercles, the tubercle bacillus 
being primarily necrotizing to the placental cells, but that the fixed 
tissue elements in the neighborhood supply cells for the tubercle. 
In the later stages of the process caseous necrosis of the tuberculous 
structures takes place, and the villi themselves suffer invasion and 
degeneration. Their blood-vessels are frequently occluded by hyaline 
thrombosis and proliferation of the endothelial lining. Tubercle bacilli 
have been demonstrated in the vessels of the fetal side of the placenta, 
though less frequently and abundantly than in the maternal vessels. 

Syphilis of the placenta may take the form of a diffuse hyperplasia, 
or of a nodular or gummatous process. The placenta is enlarged, in- 
durated, and heavy; it is light colored, in localized areas or diffusely. 
Microscopically, cellular proliferation springing from the adventitia of 
the blood-vessels is the characteristic feature. The epithelial cells 
covering the villi may proliferate, and fatty degeneration of the body of 
the villi is not infrequent. The chorion and amnion may be diffusely 
thickened. The syphilitic nature of cases conforming with the above 
description is often doubtful, as is also the nature of some of the cases of 
placentitis that are often described as syphilitic. 

HYPERPLASIA 

Occasionally, diffuse or circumscribed thickening of the decidual 
occurs in association with chronic metritis; the term endometritis 
decidualis is applied to this condition. (See Inflammation.) 



DISEASES OF THE REPRODUCTIVE ORGANS 



813 



Placental Polypi. — Portions of the decidua, and especially the 
placenta, retained in the uterus, may remain firmly attached and 
may undergo subsequent proliferative change, forming polypoid tumors 
of adenomatoid structure. These are particularly frequent after abor- 
tion. 

Destructive Placental Polyps. — Like the preceding, these orig- 
inate in retained portions of the placenta, but differ in the more 
active proliferative changes that take place. On the uterine surface 
they are covered with fibrin and blood-clots, and at their attachments 
are composed of variously formed cells, including large epithelium-like 
cells enclosed in a vascular stroma. The growth may involve the uterine 
tissues to a considerable extent. Its nature is obscure in some particu- 
lars, but resembles that of the syncytioma. 

Hydatid moles present themselves as rounded, rather trans- 
lucent bodies hanging by their pedicles to the outer surface of the 
chorion, and often attached one to another in clusters, resembling a 




Fig. 399. — Section of a hydatid mole. 



bunch of grapes. Microscopically, they are found to be composed of 
myxomatous or more or less edematous fibrous tissue containing few 
cells and free nuclei, and covered on the outer surface by epithelial 
cells (Fig. 399). The nature of the hydatid mole has been the sub- 
ject of some controversy. Virchow taught that they are simply myxo- 
matous hypertrophied chorionic villi. More recent investigators have 
found evidences of active hyperplasia of the superficial epithelium of 
the chorion villi, with secondary degeneration, edema, and necrosis. 
This accounts for the fact that sometimes the moles extend deeply 
into the decidua, and even into or through the muscular wall of the 
uterus. 

Hydatid moles are especially met with in women suffering from 
chronic constitutional diseases (nephritis, anemia) and in those becom- 



814 



A TEXT-BOOK OF PATHOLOGY 



ing pregnant late in life. Endometritis seems to bear some relation, 
though the disease is evidently one of the fetal rather than maternal 
tissues. This is shown by the limited extent of the disease in some cases, 
and by the fact that in twin pregnancy the membranes of only one of 
the fetuses may be affected. When the disease is extensive death of the 
fetus usually results, and the moles are discharged in the form above 
described, or enclosed in clotted blood. 

Syncytioma Malignum. — The nature and peculiarities of this 
condition have been sufficiently described (see page 258). 

The Penis and Scrotum 
congenital abnormalities 

Absence of the penis is rarely observed; more frequently it is abnor- 
mally small, resembling the clitoris of the female. Occasionally the 
organ is doubled, each half containing a duct, one for the discharge of 
urine, the other for seminal fluid. 

Hypospadias is the condition in which the urethra terminates in 
an orifice on the under surface of the penis, in the pendulous portion or 
at the bulb, or occasionally at the root of the scrotum or in the peri- 
neum. With hypospadias there is usually some deformity of the 
scrotum, the commonest being a division into lateral halves containing 
the testes, or the latter may be in the inguinal canal or abdomen. Epi- 
spadias is a less frequent condition; the urethral orifice in this case is 
found upon the dorsal side of the organ. Excessive length of the prepuce 
is a frequent abnormality; there may be associated with this stenosis of 
the preputial opening, so that the glans penis cannot be exposed {phi- 
mosis) . 

The condition of hermaphroditism, or the presence of the genital 
organs of both sexes in one individual, is rare, while pseudoherma- 
phroditism is more common. In the latter the genitalia are distinctly 
of one sex, although anomalous in formation, while the secondary sexual 
characters are those of the other sex. 

INFLAMMATION 

Inflammation of the mucous membrane of the glans penis 
(balanitis) or of the prepuce (posthitis) is not infrequent. Among the 
more frequent causes are uncleanliness, with decomposition of smegma 
retained beneath the prepuce, irritation by the urine in cystitis or other 
inflammatory diseases, gonorrheal infection, and chancroids. The 
mucous membrane becomes swollen and red, and considerable purulent 
exudate may be discharged. Edematous swelling of the prepuce is 
frequent, and may cause inability to retract the prepuce over the glans 
(phimosis). In other cases the prepuce, previously drawn back, be- 
comes so tensely swollen that it cannot be pushed forward to its normal 
position (paraphimosis) . 



DISEASES OF THE REPRODUCTIVE ORGANS 



815 



In catarrhal inflammation of the prepuce there may be associated 
retention-cysts of the mucous glands. The cysts may rupture, causing 
small ulcerations. The inflammation may take a membranous or 
phlegmonous form ; these may lead to phagodenic ulceration or gangrene 
and may extend to the body of the organ. 

Inflammation of the cavernous bodies may result from trauma- 
tism, or from extension of gonorrheal urethritis, and may sometimes 
occur in infectious diseases, such as small-pox, pyemia, etc. The penis 
swells considerably, and abscesses or diffuse purulent infiltration may 
result. In traumatic cases with hemorrhagic exudation necrosis or 
gangrene may result. In case of favorable termination after severe 
inflammations deforming cicatrization may occur. 

INFECTIOUS DISEASES 

Syphilitic chancres and secondary lesions and soft chancre or 

chancroid are frequently located upon the prepuce or its frenum, or 
upon the glans penis. (The lesions are described in Part I.) 

Tuberculosis is a rare condition in this situation. It has been 
met with in the form of necrotic ulcerations. It is very likely that 
direct infection of the penis may occur during coitus with a woman who 
has genital tuberculosis. In children it has been attributed to the prac- 
tice in certain rituals of smearing the wound of circumcision with saliva. 

TUMORS 

Papilloma, or condyloma acuminatum, is not infrequent on 
the glans penis and prepuce. Sometimes it has a distinctly inflam- 
matory origin, occurring in association with gonorrhea, syphilis, or 
other forms of local irritation; in other cases it originates without dis- 
coverable cause. There are usually several or many warty elevations, 
and occasionally a mass of warts is aggregated in a cauliflower fashion. 
Microscopically, condylomata are composed of a stroma of vascular con- 
nective tissue covered with hyperplastic epithelium. The cauliflower- 
form may be distinguished from epithelioma by observing that the 
mucous membrane is not infiltrated and is movable upon the underlying 
tissues. 

Carcinoma (epithelioma) of the penis may arise from the glans or 
from the prepuce. It may present itself as an infiltrating growth with 
a tendency to ulceration, or as a papillomatous, cauliflower-like growth. 
In the latter case the primary growth is either papillomatous, with sec- 
ondary carcinomatous alteration, or carcinomatous, followed by papillo- 
matous outgrowths. Considerable destruction of the glans penis may 
occur, and metastatic nodules are frequently formed in the inguinal 
glands. 

Epithelioma of the scrotum is comparatively frequent in chimney- 
sweeps and paraffin-workers. 

Elephantiasis of the scrotum is a common disease of the East. 
The scrotum may be enormously enlarged. Some cases are due to 



816 



A TEXT-BOOK OF PATHOLOGY 



filariasis; in other cases filariae cannot be demonstrated. Somewhat 
similar thickening of the prepuce is a rare condition. 

Cysts. — Small cysts, due to occlusion of the glands of the mucous 
membrane and of the skin, are occasionally met with under the prepuce 
and in the scrotum. Dermoid cysts of the scrotum are occasionally 
observed. 

Lipomata, angiomata, and fibromata are rare forms of tumors 
of the penis. 

Concretions beneath the prepuce result from phimosis with reten- 
tion of the smegma. Sometimes they increase by constant additions 
until they reach considerable size (200 g.). In one case seen by one of 
us gouty tophi in the prepuce grew to the size of a small lemon. 

INJURIES OF THE PENIS 

Direct traumatism may occasion serious laceration of the corpora 
cavernosa, especially when the penis is erect at the time of injury. 
Considerable hemorrhagic extravasation may occur, and inflammation 
or even necrosis and gangrene may ensue. Fracture of the penis is a 
term applied to rupture of the fibrous capsule of the cavernous bodies. 
Both this and less extensive lacerations occasion great hemorrhagic 
swelling, with subsequent inflammation or necrosis. Injuries to the 
penis may cause rupture of the urethra, with extravasation of urine. 

The Testicles 
anatomical and physiological considerations 

The testicles are composed of tubules lined with cells, spermato- 
gonia, from which the spermatozoa are derived, and of certain interstitial 
cells (cells of Leydig) which form a somewhat distinct glandular system. 
The sharp distinction drawn between these two components of the 
testicle by some experimenters has not been fully established. 

Aside from its relation to the reproductive function accomplished 
by the production of spermatozoa, the testicles, as the ovaries in the 
female, have an important bearing on growth and metabolism. Early 
castration leads to eunuchism, in which bodily growth, and especially 
fatty deposition, may be excessive, while infantile characteristics and 
the arrest of development of certain accessory organs of sex are marked. 
Sometimes tumors of the testicles have occasioned precocious develop- 
ment. These effects are attributed to removal or stimulation of the 
function of the interstitial cells rather than of the tubular cells. The 
adrenals, hypophysis, and pineal gland seem to exercise some influence 
upon the testicle. 

CONGENITAL ABNORMALITIES 

Absence of one or both testicles is a rare condition. More fre- 
quently the organ is hypoplastic, remaining undeveloped through life, 
the man being infantile or effeminate. Polyorchism occurs at times. 



DISEASES OF THE REPRODUCTIVE ORGANS 



817 



The most frequent congenital abnormality is cryptorchismus, a con- 
dition in which one or both testicles remain in the abdominal cavity, 
in the inguinal canal, or elsewhere in the tract through which normal 
descent occurs. The undescended testicle may descend at or before 
puberty, or may remain fixed in its abnormal position. In the latter 
case, especially if the testicle is in the inguinal canal, secondary inflam- 
mation or atrophy may occur. Slight defects in the development of the 
testicle are not infrequent, but are unimportant. The causes of cryp- 
torchismus are numerous, the most common being arrest of development, 
antenatal peritonitis, and a disproportion between the size of the organ 
and of the inguinal canal. 

ATROPHY AND HYPERTROPHY 

Atrophy may follow any form of inflammation of the testicle or 
epididymis, such as those occurring after gonorrhea, mumps, and other 
infectious diseases or traumatism. In other instances pressure upon 
the organ, as in hydrocele, tumors, etc., is the cause of atrophy. Atrophy 
also may occur in cryptorchism or when, by stricture of the vasa or 
ejaculatory ducts, semen is retained in the testes. Any of the above 
conditions, operative in early life, may lead to aspermia and sterility. 
Hypoplasia may accompany deficient thyroid or pituitary function. 
The most frequent form of atrophy is that which occurs as a natural 
process of involution in old age (senile atrophy). 

The testicle decreases in size, increases in consistency from over- 
growth of connective tissue, and is usually more pigmented than in 
health. Microscopically, the seminal tubules are found to have under- 
gone fatty degeneration and contain fatty debris and blood-corpuscles. 

Hypertrophy of one testicle may occur as a compensatory process 
in cases of disease, atrophy, or removal of its fellow, and after disease 
of the adrenal cortex. Hypertrophy of this sort has been produced 
experimentally in animals. The seminal tubules increase in size, but 
are otherwise normal. 

DEGENERATIONS 

Fatty degeneration is frequently observed in testes subjected to 
pressure through tumors or other pathological conditions, and in cases 
of atrophy of the testicle from any cause. The epithelium of the tubules 
is attacked and may be completely destroyed, with production of fatty 
detritus. 

Myxomatous degeneration occurs in various tumors of the testis 
and in gummata. 

Calcification may affect old inflammatory deposits, especially 
those of the epididymis. 

Caseation is a frequent condition in tuberculous and syphilitic 
lesions; and abscesses may undergo a process of inspissation, with 
formation of dry, caseous material. 

52 



818 



A TEXT-BOOK OF PATHOLOGY 



CIRCULATORY DISTURBANCES 

Active hyperemia of the testis, epididymis, and especially of the 
membranes, occurs in association with acute inflammations. 

Passive hyperemia is caused by pressure upon the veins or dis- 
ease of the veins (varicosity) . The testis and epididymis become swollen 
from edema, and, if the hyperemia persists, fatty degeneration and 
atrophy may result. Serous effusion into the tunica vaginalis (hydro- 
cele) may be purely dropsical, but is more frequently inflammatory 
(see page 820). 

Embolism of the spermatic artery may occasion hemorrhagic 
infarction, followed by necrosis or gangrene of the testis. This sequence 
has been observed in a few cases, and has been proved experimentally. 
Sometimes gangrene seems to be caused by phlebitis of the pampiniform 
plexus. 

INFLAMMATION 

Inflammation may involve the testis (orchitis), the epididymis (epi- 
didymitis), or the tunica vaginalis (vaginitis testis). 

Etiology. — Traumatism is a frequent factor in the etiology, and 
causes inflammation of the epididymis and membranes more frequently 
than of the testicle itself. Blows, bruises, and contusions are the usual 
conditions that cause this form of inflammation. 

In another group of cases the irritants are micro-organisms con- 
veyed through the blood. Thus in typhoid fever, tuberculosis, pneu- 
monia, and various forms' of septicopyemia the specific organisms 
have been discovered in the areas of inflammation. Similar inflamma- 
tions occur in mumps, scarlet fever, and small-pox, and are doubt- 
less caused in the same way, though the specific organisms are un- 
known. In these cases the testis is more frequently affected than the 
epididymis. 

In a third group of cases infection occurs through the vas deferens, 
and the epididymis is affected first and often alone. The most fre- 
quent infectious agent in this group of cases is the gonococcus; but 
other micro-organisms may enter the vas deferens, reach the epididymis 
and cause inflammation, in other diseases of the bladder or urethra, 
or after operations upon these parts, such as crushing vesical calculi, 
cutting urethral strictures, and the like. 

Pathological Anatomy. — Inflammations of the different parts 
may be separately considered. 

In acute orchitis the testis is more or less edematous and swollen 
on account of inflammatory exudation. Microscopically, the strik- 
ing feature is round-cell infiltration of the intertubular tissues. This 
may be diffuse and uniform, or may occur in circumscribed areas, the 
latter being especially common in the orchitis of variola and pyemia. 
The round cells may infiltrate the walls of the tubules, and may be 
discharged into the tubules in great numbers. At the same time the 
epithelial cells may suffer degeneration and desquamation. Intense 



DISEASES OF THE REPRODUCTIVE ORGANS 



819 



orchitis may lead to the formation of abscesses, single or multiple. 
These may subsequently undergo complete absorption, or may become 
inspissated and encapsulated, the contents of such a focus consisting 
of fatty detritus and cholesterin. In other cases the abscess may 
rupture externally, and occasionally granulations springing from the 
tunica albuginea or the testis may protrude through the opening. The 
term benign fungus is applied to this condition. 

Chronic orchitis usually results from the acute form. The inflam- 
matory changes of the intertubular tissues gradually lead to indura- 
tion, and the testis becomes hard and contracted, the connective tissue 
and septa being increased in density, the tubules at the same time suffer- 
ing degeneration and atrophy. In cases following acute suppurative 
orchitis the tissues surrounding the inspissated abscess become sclerotic, 
and the tubules are in large part or wholly destroyed. Small nodular 
areas are discovered in such cases, and on section these are found to 
consist of a dense wall of fibrous tissue enclosing thickened pus contain- 
ing fatty detritus and cholesterin. The membranes surrounding the 
testis are usually thickened and united by adhesions. 

Chronic orchitis without a definite antecedent acute stage is a fre- 
quent result of syphilis (see page 821). 

Acute epididymitis occurs when infective agents have reached the 
epididymis through the vas deferens. There is tense swelling of the 
epididymis, and not rarely associated inflammation with serous exuda- 
tion in the tunica vaginalis. The testis is not, as a rule, involved. 
The process begins as an acute catarrhal inflammation of the tubules 
of the epididymis; later, cellular infiltration and occasionally abscess- 
formation occur in the intertubular connective tissues. The inflam- 
mation is sometimes completely resolved, but in other cases fibrous 
thickening, diffuse or nodular, results. Inspissated abscesses surrounded 
by fibrous tissue are sometimes seen, as in orchitis. The epithelium of 
the tubules embedded in the new-formed fibrous tissue may undergo 
a certain amount of proliferation, suggesting the appearance of adenoma 
or cancer. The vas deferens may be permanently obstructed, and the 
tubules on the proximal side and in the testis may undergo cystic dis- 
tention. Extensive epididymitis very commonly causes atrophy of the 
testis. 

Vaginitis testis and periorchitis are terms applied to inflammation 
of the tunica vaginalis testis. This condition is usually the result of 
orchitis or epididymitis, but may sometimes occur as a primary inflam- 
mation resulting from traumatism or other forms of irritation. 

The tunica vaginalis is a reflection of the peritoneum, and inflam- 
matory conditions arising in it resemble those of the abdominal peri- 
toneum. 

Serous or serofibrinous vaginitis testis is the most frequent form. 
This may be acute or chronic, and is characterized by the accumula- 
tion of small or large collections of serous liquid. In slowly developed 
cases, the quantity of liquid may be one or two liters. It may be clear 
serum, but often contains flakes of fibrin or leukocytes,, and is sometimes 



820 



A TEXT-BOOK OF PATHOLOGY 



reddish from the presence of red blood-corpuscles. Sometimes the liquid 
is milky or turbid, and contains fat-droplets and cholesterin crystals. 
A chylous variety occurs in tropical countries, and is probably caused 
by the Filaria sanguinis hominis. 

Hydrocele is the term used to designate effusions of these sorts. 
Sometimes the liquid contains spermatozoa, when the term hydrocele 
spermatica is applied. This conditions is due to the escape of spermato- 
zoa from improperly developed spermatic tubules or from ruptured 
cysts of the epididymis or testis. In certain cases it is difficult to dis- 
tinguish hydrocele spermatica and spermatocele (see page 823). 

When hydrocele persists the tunica vaginalis undergoes hyperplastic 
thickening, and small, wart-like elevations may be formed (periorchitis 
prolifera). These nodules may become separated and remain in the 
sac as free bodies, like those in the joints. Another result of the second- 
ary inflammatory changes in the membrane is adhesion of the reflex- 
ions, causing a bilocular or multilocular hydrocele. 

When the canal connecting the sac with the peritoneal cavity has 
remained patulous the fluid of hydrocele may be pressed into the ab- 
dominal cavity. The term hydrocele processus vaginalis is applied to 
such cases, and the term hydrocele funiculi spermatid to cases in which 
only the upper part of the vaginal canal is patulous and filled with 
liquid. Hydrocele funiculi cystica results from collections of fluid in 
the middle portion of the canal, the upper and lower ends being oblit- 
erated. 

Purulent vaginitis testis occurs in association with epididymitis and 
orchitis, and sometimes primarily after traumatism. An ordinary 
hydrocele may be converted into a purulent collection by puncture with 
infected instruments. The sac is more or less distended with purulent 
liquid, and the surface of the membrane is covered with fibrinopurulent 
exudate. The pus may discharge externally, or may become inspis- 
sated; and extensive adhesions may obliterate the sac. 

Hemorrhagic Vaginitis Testis. — In severe acute inflammations the 
exudation may be more or less hemorrhagic. More distinctly hemor- 
rhagic forms of inflammation result from traumatism; in these cases 
there is first extravasation of blood and then inflammation. The sac 
may be lined with fibrinous and hemorrhagic deposits while the mem- 
brane itself is infiltrated and opaque. In the terminal stages consider- 
able thickening and sometimes calcification of the tunica vaginalis are 
observed. 

Inflammation of the vas deferens may be associated with epi- 
didymitis or orchitis, or may occur independently in cases of direct 
traumatism. In syphilitic disease of the testis, and less commonly in 
other forms of orchitis, the vas deferens may be greatly thickened. 

Varicocele is a tumor made up of dilated vessels of the pampiniform 
plexus and spermatic veins. It is due to obstruction of the venous 
flow by foreign masses, or the cases arising without such reason are 
ascribed to the weight of the blood column upon vessels with poor walls 
and valves. It is commonest in the young, and appears most often on 



DISEASES OF THE REPRODUCTIVE ORGANS 



821 



the left side. The left spermatic vein empties at right angles into the 
renal vein, so that there is in this vessel a long column of blood in an 
almost directly vertical position. 

INFECTIOUS DISEASES 

Tuberculosis is most frequent in the epididymis, but may involve 
the testicle as well. The infection occurs in one of two ways: either 
through the vas deferens, in consequence of tuberculosis of the prostate, 
seminal vesicles, or bladder; or through the circulation in cases of pul- 
monary or other forms of tuberculosis. It has been shown that tubercle 
bacilli are discharged from the body in the seminal fluid in cases of 
pulmonary and other forms of tuberculosis; and when local conditions 
predispose tuberculous infection of the 
epididymis may occur. Gonorrheal epid- 
idymitis seems to constitute such a local 
predisposition. Primary hematogenous in- 
fection of the epididymis seems to occur in 
rare cases. 

In cases of infection through the vas 
deferens there are formed in the walls of 
the tubule of the epididymis small tubercu- 
lous masses, which rapidly increase in size 
and run together, forming caseous areas of 
considerable size. Further invasion occurs 
along the lymphatic channels and the 
tubules, and rapid involvement of a con- 
siderable part of the epididymis results 
(Fig. 400). The tubule surrounded by 
tuberculous tissue may become filled with 
desquamated epithelium and puriform or 
caseous matter, and mav be dilated in a Fig. 400.— Tuberculosis of the 

. ' ^ epididymis and testicle (modified 

cystic form. Extension to the testicle may from Bollinger), 
occur, but is unusual. 

Associated serous or serofibrinous vaginitis testis is not infrequent; 
and in some cases the tuberculous disease itself extends to the testicular 
envelopes and causes nodular elevations, or ulcerations and fistulous 
communications with the surface. 

Hematogenous tuberculosis of the epididymis is, in the first place, 
of the miliary form, but the tubercles grow rapidly and caseous nodules 
are rapidly formed. 

Tuberculosis of the vas deferens may be secondary to tuberculosis 
of the seminal vesicles and bladder, or of the epididymis. It is charac- 
terized by caseous swelling of the walls of the duct. 

Syphilis is not infrequently seen in the testicle in the late stages 
of acquired syphilis and in congenital syphilis. The epididymis and 
the membranes are secondarily involved. Two forms may be dis- 
tinguished. The more frequent is that in which diffuse induration of 




822 



A TEXT-BOOK OF PATHOLOGY 



the testicle occurs; in the less frequent variety there are circumscribed 
gummata. In the diffuse form the organ is more or less uniformly 
indurated, and on section dense bands of fibrous tissue are conspicuous. 
The tubules suffer compression, degeneration, and atrophy, and some- 
times become converted into cheesy foci. The gummata have the 
usual translucent or cheesy appearance. When the membranes are 
involved diffuse thickening occurs; and in rare cases the disease extends 
to the skin, causing superficial granulations (syphilitic fungus). The 
vas deferens is often greatly thickened, as are also the walls of the blood- 
vessels of the testis and epididymis. 

Lepra of the testis occasions nodular lesions and pressure-atrophy 
of the tubules. Lepra-cells containing bacilli, as well as free bacilli, 
occur in the tubules in abundance. This fact is important as indicating 
a possible mode of transmission of the disease. 

TUMORS 

Fibroma is occasionally observed in the rete testis and tunica 
albuginea as a small nodular tumor. 

Chondroma is rare. It may occur in the epididymis or rete, as a 
single node or as multiple small nodules. Osteoma is very rare. 
Myxoma is rare, except in association with other tumors. Rhabdo= 
myoma sometimes occurs in the form of flesh-like growths of the testis. 
None of the above occur frequently in pure form, being usually com- 
bined in various mixed tumors. 

Sarcoma may occur in any of its various forms in the testis, and 
less commonly in the epididymis. The supporting tissue between the 
tubules is its usual starting place, but the "interstitial cells" are believed 
by some to be capable of sarcomatous growth. Sarcoma forms rapidly 
growing whitish or reddish tumors. Secondary changes, such as fatty 
degeneration, hemorrhage, cystic softening, and caseation, are not infre- 
quent. Cystic dilatation of the seminal tubules may occasion marked 
changes in the appearance of the tumor. The cysts are small, and filled 
with turbid liquid containing fat, desquamated cells, and cholesterin; 
or large, and contain serous liquid, either clear, turbid, or blood-tinged. 
The lining epithelium of the cysts is columnar, or, in case of cysts of the 
epididymis, often ciliated. The walls of the tubules in some instances 
undergo active hyperplasia, giving rise to papillomatous elevations of 
the inner surface, and a truly adenomatous proliferation may occur. In 
the latter cases the tumor may be designated adenosarcoma. Growths 
of this variety are sometimes met with in young adults or children, and 
most frequently in the rete testis. They are more or less malignant, 
causing frequent metastasis along the lymphatics or blood-vessels. Sar- 
comatous change is not infrequently seen in congenitally misplaced 
testes. 

Adenoma of the testicle is rare; much more frequently cystic 
tumors have a more or less adenomatous character (see Cysts). 

Carcinoma usually appears in the testes and epididymis in a 



DISEASES OF THE REPRODUCTIVE ORGANS 



823 



medullary form, but occasionally a scirrhous growth occurs (Fig. 
401). Mucoid and colloid degenerations are rather frequent, and 
cystic softening may occur. Cysts may also result from dilatation of 
the tubules. Cartilaginous areas are sometimes found in the stroma 
of the growth; to such the term chondrocarcinoma is applied. More or 
less complete destruction of the testicle and epididymis is frequent, 
but the tunica albuginea usually resists invasion for a considerable 
time. Carcinoma of the testicle seems to originate from the epithelium 
of the convoluted tubules. Metastasis through the lymphatics and 
blood-vessels is frequent, and extension through the testicular envelopes 
to the skin may occur; spread may follow the vas deferens to the retro- 
peritoneal tissues. 

Teratomata and mixed tumors 
are common in the testicle. The 
most important of the former is 
the chorion epithelioma, while of 
the latter many combinations ap- 
pear, cystic rhabdomyoma perhaps 
being the most frequent. 

Cysts. — Retention-cysts of the 
tubules are frequent in cases of in- 
flammation and induration of the 
testis and epididymis. Sometimes 
they contain a simple milky liquid; 
in other cases spermatozoa are 
found in the fluid, and to these 
cysts the term spermatocele is ap- 
plied. The cysts may be numerous 
and small, or may be very large, 
containing a hundred or more cu- 
bic centimeters of liquid. The cysts 
are found in the body of the organ; 
but, when large, project from the 
surface. Very large cysts push the 

testicle and epididymis to one side. (f rom a specimen in the Museum of the 

Occasionally, cysts originate from Philadelphia Hospital), 
the hydatids or the paradidymis. 

These may be spermatoceles, when one of the vasa aberrantia opens 
into them. 

Secondary proliferations of the epithelium of the cysts may convert 
a simple into a papuliferous cystoma; and occasionally the primary 
process seems to be one of adenomatous character, the cystic condition 
being the result of secondary distention or of the peculiar character of 
the acini formed. 

Small cystic cavities may contain mucous liquid or thick, curdy 
material. In the latter case the term atheromatous cyst is applicable. 

Dermoid cysts are occasional tumors of the testis proper. They 
may be simple sacs, lined with epidermal tissue and filled with pulta- 




824 



A TEXT-BOOK OF PATHOLOGY 



ceous matter; or complicated dermoids, containing teeth, bone, muscle- 
fibers, and nerve tissue. 

PARASITES 

Echinococcus cysts are encountered on rare occasions. 
The Prostate Gland 
inflammation 

Inflammation of the prostate, or prostatitis, is most frequently 
secondary to posterior urethritis. Sometimes, however, it occurs in 
other ways, such as metastatic involvement in general pyemia or other 
forms of infection. Inflammations in the vicinity and direct injuries 
of the prostate may likewise cause acute inflammation. 

Pathological Anatomy. — A simple and a suppurative form may 
be distinguished. 

Simple Prostatitis. — In the ordinary prostatitis following urethritis 
the disease takes the simple form, the gland being congested and swollen 
and causing by its enlargement more or less obstruction of the urethra. 
Small suppurative foci may be formed in and about the glandular 
pouches and tubules. Catarrhal changes are seen in the tubular 
mucosa. 

Suppurative or phlegmonous prostatitis, or abscess of the prostate, 
may be a terminal condition of the previous form, or it may be developed 
primarily. In cases of metastatic prostatitis a number of foci of sup- 
puration may occur and subsequently coalesce, or a diffuse suppurative 
infiltration may take place. The development of abscesses is usually 
acute, though in some cases it may occur insidiously. If the abscesses 
are small they may subsequently undergo encapsulation, inspissation, 
and even calcification. Larger abscesses are prone to rupture into the 
urethra, usually through a number of openings. Sometimes, however, 
the inflammation extends to the tissues around the gland, causing peri- 
prostatitis, and later rupture into the rectum may occur. Extensive 
phlegmonous inflammation of the pelvic tissues is an unusual result. 

Chronic prostatitis is usually a companion of long-standing gonorrhea, 
and may assume a catarrhal or interstitial form. The catarrhal is more 
common, but there is always some indurative change. There is a thick, 
mucopurulent secretion in the tubules, which may dilate or coalesce 
by degenerative softening of the interstitial tissue. 

ATROPHY AND DEGENERATION 

Atrophy of the gland is occasionally met with in youthful indi- 
viduals, and may be the result of disease or removal of the testis. It 
also occurs in the aged, and in this case atrophy of the tissues surround- 
ing the prostatic ducts may be accompanied by dilatation of the ducts 
themselves, the gland then presenting a cavernous appearance. Atrophy 
of the gland sometimes leads to incontinence of urine. 



DISEASES OF THE REPRODUCTIVE ORGANS 



825 



Fatty degeneration of the epithelium of the gland and of the 
muscle-fibers is frequent in old age, and may occur as an independent 
condition or in association with hypertrophic enlargement of the gland. 
The gland becomes soft and diffusely yellow or mottled in color. 

CONCRETIONS 

Prostatic concretions are not unusual in persons of advanced age, 
and are frequently found in considerable numbers. They vary in size 
from almost microscopical granules to bodies the size of a millet-seed. 
They may be colorless at first, but usually become brownish. On sec- 
tion through the gland these brownish-colored bodies give the appear- 
ance of a surface sprinkled with snuff. The granules are usually round 
or oval, and are characterized by concentric lamellations. The term 
amylaceous bodies has been applied to them, and they have been sup- 
posed, though erroneously, to be composed of amyloid material, such as 
occurs in amyloid degeneration. Sometimes they reach considerable size, 
when calcareous salts deposit around them and give them an irregular 
form. Sometimes the concretions are discharged through the prostatic 
ducts into the urethra; in other cases the larger concretions project 
prominently into the urethra beneath its mucous membrane. 

INFECTIOUS DISEASES 

Tuberculosis of the prostate is usually found in association with 
tuberculosis of the other genital organs, especially the vas deferens and 
epididymis. It is also met with in association with tuberculosis of the 
bladder or kidney. The prostate is usually diffusely enlarged, and may 
be somewhat nodular upon the surface. On section caseous areas are 
found, or the entire gland has a caseous appearance. Recent tubercles 
are rarely visible, as caseation progresses with unusual rapidity in this 
organ. Primary tuberculosis of the prostate is rare. 

HYPERTROPHY AND TUMORS 

Hypertrophy of the prostate is a condition of clinical and patho- 
logical importance because of its common appearance after the age of 
fifty, the frequency of consequent cystitis and ascending infections, and 
the invalidism it occasions. Practically all hypertrophies of the pros- 
tate will fall into two divisions: first, those due to inflammatory dis- 
ease, either primary or by obstruction and extension from the urethral 
outlets of the gland, and, second, those due to a more or less distinct 
tumor growth of some of the constituent tissues of the organ. In some 
cases chronic posterior urethritis seems to be the important factor; in 
other instances disturbances of the circulation, and especially varicose 
conditions of the veins, are active in the causation. 

The organ may enlarge in a uniform manner, or there may be nodular 
or localized swelling. Of the localized form the most important, from a 



826 



A TEXT-BOOK OF PATHOLOGY 



clinical aspect, is that in which the middle lobe or the isthmus of the 
gland enlarges and projects under the posterior wall of the urethra as a 
small or large rounded elevation, or as a transverse bar or obstruction 
(Fig. 402). According to the investigations of some authorities, the 
enlargement in such instances is due to a hyperplasia of accessory pros- 
tatic tissue lying immediately under the mucous membrane of the 
bladder and of the prostatic portion of the urethra, with subsequent 
involvement of the isthmus of the gland itself. 




Fig. 402. — Hypertrophy of the prostate. Seen from within bladder. 

On section through the gland there may be a uniform induration, 
or in other cases, in consequence of associated changes in the epithelium 
or acini, there may be scattered through the gland areas of softening or 
of proliferation of the glandular elements, or cystic distentions of the 
gland tubules. In such instances the indurated gland presents more or 
less softened or cystic foci. 

Microscopically, in the diffuse form, involving the stroma alone, 
the gland presents merely the features of uniform fibromyomatous 
proliferation, and corresponds in structure with fibromatous or myo- 



DISEASES OF THE REPRODUCTIVE ORGANS 



827 



fibromatous tumors of the uterus (Fig. 403). In other cases the glandu- 
lar elements take an active part in the pathological process, and a dis- 
tinctly adenomatous character is added. There is usually some inter- 
stitial round-cell increase, a condition suggesting that inflammatory 
lesions are associated, whether or not they are primary. The glandular 
elements may undergo fatty degeneration, and the lumina of the acini 
and tubules may be filled with milk-like, fatty material. In other cases 
pronounced cystic distention of the gland occurs. 

Results of Hypertrophy of the Prostate. — Enlargements of the 
prostate usually interfere with the discharge of urine. This is particu- 
larly marked in cases in which the middle lobe projects into the urethra, 
though in some instances the opposite result may be produced, viz., 
incontinence of urine due to interference with the contractions of the 




Fig. 403. — Section of hypertrophied prostate of a man aged seventy-four years; natural 
size: a. Urethra; 6, colliculus seminalis (Soein). 

sphincter of the neck of the bladder. In cases of enlargement of one of 
the lateral lobes obstruction to the flow of urine is caused by lateral 
deviation and compression of the urethra. Upward and forward pro- 
jection of the middle lobe forms a reservoir in the postero-inferior part 
of the bladder, where fermentation and infective cystitis may begin. 

The muscular walls of the bladder at first become hypertrophied, 
but dilatation of the bladder subsequently occurs. Cystitis, distention 
of the ureters and renal pelves, and ascending infection, causing ureter- 
itis, pyelitis, and pyelonephritis, are among the late results. 

Sarcoma is a rare tumor of the prostate. It generally has the char- 
acters of lymphosarcoma, and is a rapidly growing, destructive tumor. 
In some cases combination with adenoma has been observed. Sarcoma 
is, indeed, rarely pure in type, myomatous elements being commonly 
present. This tumor is commonest in childhood. 



828 



A TEXT-BOOK OF PATHOLOGY 



Carcinoma of the prostate is more frequent than sarcoma, though 
it is not a common tumor. The tumor arises from the epithelium of the 
tubules, and takes the form of nodular, grayish or white masses which 
cause irregular enlargements of the gland, and not rarely project into 
the urethra or the base of the bladder. The cells of prostate cancers 
are quite small and stain rather deeply, giving an impression of sarcoma 
cells. Superficial ulceration of the mucous membrane over these pro- 
jections is not infrequent. The stroma of the gland usually proliferates 
actively. Metastasis to the inguinal glands, or to distant parts, espe- 
cially the bones, is not infrequent; but direct extension to the bladder, 
seminal vesicles, or rectum is more common. There may be frank 
adenomata of the prostate ; these are usually associated with or the cause 
of "hypertrophy." 

Cysts of the prostate are usually the result of retention of exudates 
within the glands or their ducts. Occasionally, cystic formations seem 
to arise from remnants of Miiller's ducts. 

Cowper's Glands 

Inflammatory conditions are met with in these glands in association 
with similar affections of the prostate. Occasionally, independent in- 
flammation of Cowper's glands results from posterior urethritis. The 
gland is enlarged and presents the usual appearances of inflammation. 
The termination may be abscess-formation. Obliteration of the mouths 
of the ducts may occasion cystic conditions in the glands, and carcinoma 
has been described. 

The Seminal Vesicles 

Inflammation. — Acute inflammation of the seminal vesicles may 
occur in association with gonorrheal urethritis. The vesicles become 
distended with seminal secretion and mucopurulent exudate. Their 
walls are swollen, and the mucous membrane presents the appearance 
of catarrhal inflammation. 

Chronic inflammation may result from the acute form; it causes con- 
traction and thickening of the walls. 

Tuberculosis of the seminal vesicles is common in cases of uro- 
genital tuberculosis. The vesicles are rarely independently affected. 
The walls become thickened and may present nodular, cheesy masses, 
and there may be ulcerations of the mucous surface. The cavities of 
the vesicles contain caseous or puriform material. 

Tumors. — Primary carcinoma has been described; but secondary 
carcinoma, resulting from extension of cancer of the adjacent structures, 
is more common. 

Cystic distention and the formation of diverticula result from obstruc- 
tions of the ejaculatory duct. The contents of the vesicles in such cases 
are seromucous in character. 

Concretions frequently result from calcification of inflammatory 
exudates. They are especially frequent in association with tuberculosis. 



DISEASES OF THE REPRODUCTIVE ORGANS 



829 



The Mammary Glands 

congenital abnormalities 

Absence of one or both breasts may occur in association with other 
defects of development of the thoracic walls. Incomplete development 
of the mammary glands, or hypoplasia, may be associated with hypo- 
plasia of the genital organs. 

Supernumerary mammary glands are frequently observed; 
the term polymastia is given this condition. The supernumerary gland 
or glands may be situated between the normal glands, below these, or 
in distant parts, such as the back, shoulders, and arms. They may occur 
in either sex, and may be structurally complete and functionally active; 
or may be merely rounded masses of mammary tissue without excretory 
ducts or nipples. In the latter instances the probable explanation of the 
condition is that in the process of development parts of the normal glands 
have been split off and have separately developed. 

Early Development. — The mammary glands may be developed 
at an abnormally early period, in association with early development 
of the genital organs. 

Abnormal functional activity (secretion) may be stimulated by 
various diseases of the genital organs; and in the newborn of either sex 
during the first week of life slight secretion of colostrum-like material is 
frequent. 

Abnormal development of the male breast is occasionally 
observed, especially about the age of puberty, and sometimes copious 
secretion of milk takes place. Usually the organ subsequently atrophies, 
but exceptionally the enlargement and secretion persist. 

CIRCULATORY DISTURBANCES 

Hyperemia occurs during the menstrual period and at the beginning 
of lactation, as a physiological process, and causes slight swelling and 
redness. Pathological hyperemia plays a part in the process of inflam- 
mation. 

Hemorrhages are usually the result of traumatism. They may 
occur into the gland itself, or into the connective tissue in front of or 
behind the gland. Occasionally, hemorrhages are due to intense inflam- 
mation or to tumor-formation. The blood may find its way into the 
lactiferous tubules, and may be in part discharged from the nipple. 
In case of large hemorrhages the blood may subsequently undergo 
absorption or inspissation, and hemorrhagic cysts may be formed. 
Occasionally, hemorrhage occurs in the mamma and from the nipple at 
the time of the menses, as a form of vicarious menstruation or in cases 
of dysmenorrhea. 

INFLAMMATIONS 

Acute inflammation of the mammae, or acute mastitis, is 

rarely met with, excepting during the puerperium. Exceptionally it 
may occur in cases of general pyemia, or in the newborn as a result 



830 



A TEXT-BOOK OF PATHOLOGY 



of active secretion and obstruction to the outlets. Sometimes inflam- 
mation of the glands results from direct extension of inflammatory 
processes of the skin, subcutaneous tissue, or thoracic walls. Puer- 
peral mastitis is infective in character, and results from injury or disease 
of the nipple, through which the infective agents enter the glands. The 
actual portal of entrance may be the discharging tubules, or fissures 
and erosions of the nipple. Various micro-organisms have been dis- 
covered, including staphylococci and streptococci, of which the latter 
is the more common, especially in the puerperium. 

Thelitis, inflammation of the nipple, is common in nursing women 
when they are at all uncleanly, since the act of sucking favors the pro- 
duction of small wounds. The inflammation of the mamma following 
thelitis is usually catarrhal, but may be interstitial. 

Pathological Anatomy. — The gland is swollen and distends its cap- 
sule tensely, the skin is reddened, and a general hyperemia of the gland 
is noted. During the earlier stages the inflammation may be localized 
or may be diffuse. In the former case more or less circumscribed indura- 
tion is discovered, while in the latter the organ is uniformly indurated. 
The tendency of mastitis is to terminate in suppuration. On section 
through the gland areas of light-yellowish color indicate the purulent 
infiltration, while in the later stages more or less extensive abscesses are 
formed. The latter may communicate with the lactiferous tubules, 
and pus and milk may be discharged from the nipple. The abscesses 
tend to extend in various directions, and may finally rupture upon the 
surface through fistula?. After discharge of the pus granulation 
tissue is formed, and the cavities are obliterated by cicatricial tissue. 
When the larger discharging tubules are opened by the abscesses fistula? 
may be formed, which continuously discharge milk. Small collections 
of pus may become encapsulated and inspissated, being converted into 
cheesy or partly calcified matter. 

The connective tissues around the mammary gland are sometimes 
involved by extension, and suppurative or necrotizing perimastitis, or 
retromammary abscess, results. Extension to the thoracic walls and 
pleura is rare. 

Chronic Mastitis. — Diffuse induration of the mammary gland, 
resembling in its histological features the indurative or chronic inter- 
stitial inflammations of other organs, is occasionally seen in middle-aged 
or old women. The causes are obscure, and it is difficult to distinguish 
some of the cases from certain forms of fibromatous tumors. The gland 
becomes hardened and sometimes slightly increased in size. In other 
cases retraction of the connective tissue causes a reduction in the size. 
On section firm bands of connective tissue are conspicuous, and the 
lactiferous tubules may be distended, forming small or large retention 
cysts. This form of disease will be further discussed under Fibroma. 

ATROPHY AND HYPERTROPHY 

Atrophy of the gland occurs as a physiological process after the 
menopause, or it may result from local causes, such as abscess or tumor- 



DISEASES OF THE REPRODUCTIVE ORGANS 



831 



formation. Artificial menopause, following oophorectomy or diseases 
of the reproductive organs, may occasion atrophy similar to that nor- 
mally present in old age. The gland may simply decrease in size, with- 
out notable change of any other kind. Sometimes, however, connective- 
tissue hyperplasia accompanies the atrophy of the glandular elements, 
and diffuse infiltration may occur. 

Hypertrophy of the gland is sometimes met with in girls at the 
age of puberty, and leads to a uniform enlargement of the organ. In 
some cases there is a true hypertrophy of all the constituents of the 
gland; in other instances dilatation of the lymphatic channels, or 
degenerative changes, may cause a simulation of true hypertrophy. 
Both breasts, as a rule, are affected, and there may be increased func- 
tional activity (galactorrhea). Vicarious hypertrophy of one breast 
may occur after loss of the other. 

DEGENERATIONS 

Fatty infiltration, or lipomatosis, of the gland may accompany 
atrophy of the secreting tissue, or may occur as an independent con- 
dition. The gland may be greatly enlarged. Accompanying this 
infiltration there is usually diffuse hyperplasia of the connective 
tissue. 

Myxomatous degeneration may be associated with fatty infil- 
tration. 

INFECTIOUS DISEASES 

Tuberculosis of the mammary gland may be associated with 
tuberculosis of the axillary glands, or of other parts, or rarely may be 
primary. The tubercle bacilli reach the gland either through the lactif- 
erous tubules or through the blood. The disease is characterized by the 
formation of distinct tubercles, which tend to unite and form caseous 
areas. There is rarely extensive disease. 

Syphilis, in the form of gummata, is sometimes met with in acquired 
or congenital syphilis. Chancres or mucous patches may occur on the 
nipple. 

TUMORS 

Fibroma may be met with in the form of circumscribed nodular 
growths, or, according to the view of some pathologists, as a diffuse 
process. Circumscribed fibroma presents itself as a hard, nodular 
tumor, often having a distinct capsule, and on section presenting a 
lamellar arrangement. The glandular elements of the organ in the area 
of invasion may undergo secondary hyperplasia, and thus a form of 
fibro-adenoma may be developed. In the cases termed diffuse fibroma 
the entire organ may be indurated, or nodular areas of sclerosis may be 
found in various parts of the gland. The fibrous tissue may appear 
around and compress the glandular structures (pericanalicular fibroma), 
or the acini and ducts may at the same time undergo proliferation, 



832 A TEXT-BOOK OF PATHOLOGY 

forming adenomatous structures; or compression of the ducts may lead 
to retention cysts (cystadenofibroma) . It is difficult to determine in 
some cases whether the process is one of tumor-formation or one of 
inflammatory hyperplasia. 

A form of particular interest is that known as intracanalicular 
fibroma. In this the proliferating fibrous tissue projects into the 
normal or dilated tubules in the form of papillary ingrowths. The 
mucosa lining the tubules is pushed forward by the ingrowths, and 
covers these in the same manner as epithelium covers superficial papil- 
lomata of the skin or mucous membranes. At times the epithelium 
proliferates extensively; this may be due to inflammation or to an 
adenomatous change in the mucosa. The gland may be greatly en- 




Fig. 404. — Intracanalicular fibroma of the mammary gland (Kaufmann). 



larged, and on section presents an appearance resembling that of a cut 
through a cauliflower (Fig. 404). 

Lipoma of the mammary glands occurs in the form of round, 
encapsulated tumors of the interstitial or periglandular connective. 

tissues. 

Myxoma may occur in a diffuse form, causing a transformation 
of the gland into myxomatous material, or as circumscribed tumors. 

Myomata containing smooth muscle-fibers, and mixed tumors 
containing striated muscle-fibers, are rare. 

Chondroma and osteoma have been observed. 

Sarcoma is most frequently of the round-cell variety. It occurs 
in a diffuse form or as circumscribed nodules; association with fibroma 
and myxoma is not infrequent. 

In diffuse sarcoma the gland undergoes a uniform enlargement, 
and the neoplasm extends rapidly, forming attachments to the skin 



DISEASES OF THE REPRODUCTIVE ORGANS 



833 



and sometimes causing superficial ulceration. In other cases extension 
toward the chest walls may occur, finally involving the pleura. On 
section through the gland a lobular character of the tumor may be 
recognized, and areas of fibrous or myxomatous character are visible 
here and there. Cystic conditions, sometimes met with, may be due to 
obstruction and consequent distention of the lactiferous tubules. The 
term cystosarcoma is appropriately applied to such cases. The sarcoma- 
tous tissue may project into the dilated tubules in a polypoid form 
{intracanalicidar sarcoma). Section through the gland in such cases 
presents an appearance not unlike the surface of section of a head of 
cabbage. Cysts may also be formed in sarcomata by degenerative 
softening. 

Localized sarcomata occur as nodular tumors arising from the con- 
nective tissue surrounding the acini. On section through the tumor 
the glandular acini may be seen within the nodules. 

In any form of sarcoma the epithelium of the tubules and acini 
may undergo secondary proliferation, when the term adenosarcoma is 
applicable. 

Adenoma. — Most of the tumors of the mammary gland are asso- 
ciated with some change in the secreting tissue, and it is often difficult 
to estimate how large a part this plays in the new growth. Degenera- 
tion or hyperplasia of the epithelium and obstruction of the lumen are 
the common alterations. Constriction of the ducts leads to cyst forma- 
tion, and the process is little different when caused by chronic inflam- 
mation or neoplasms. In the tumors beginning as adenomata or with 
this type dominant, the acinous grouping is retained in those parts not 
becoming cystic, while in sarcoma or carcinoma any progressive change 
in the acini is atypical. 

Adenoma of the mammary glands may be an independent growth, 
or may be associated with fibroma, sarcoma, or other tumors. The 
independent form presents itself as a circumscribed, encapsulated, 
nodular tumor, somewhat firmer than the substance of the normal 
gland. Microscopically, adenoma follows the tubular or acinus archi- 
tecture, there being increase of the ducts or secreting areas respectively. 
These are usually somewhat dilated, and the epithelial cells are larger 
than those of the normal gland (see Fig. 81). Instead of a single layer 
of columnar cells, active hyperplasia may cause a complete filling of the 
acinus or duct with epithelium. Fatty degeneration of the cells is not 
infrequent, and sometimes there is a certain amount of milk-secretion, 
causing additional distention of the cavities. Great distention of tubules 
and acini produces cystadenoma. Papillary outgrowths of the mucosa 
taking place within dilated ducts or acini give rise to papillary 
cystadenoma. 

Carcinoma may develop from the tubules or from the acini of the 
glands. It may begin as an adenomatous tumor, which subsequently 
undergoes carcinomatous transformation, or may be a typical glandular 
cancer from the beginning. In the cases primarily adenomatous the 
structure of the acini becomes atypical and the epithelial cells tend to 

53 



834 



A TEXT-BOOK OP PATHOLOGY 



penetrate the membrana propria and form irregular collections or 
columns in the interstitial tissue. Degenerative changes are often ob- 
served, among which fatty degeneration is most frequent. Mucoid 
degeneration and a form of caseation are sometimes met with, and calci- 
fication may take place in the interstitial tissues. Occasionally an 
attempt at formation of milk occurs in the cancer-acini. 

Varieties. — Among the varieties of carcinoma are the squamous, 
medullary, the simple, the scirrhous, the myxomatous, and the so-called 
adenocarcinoma . 

The squamous carcinoma begins as an epithelioma of the nipple, or 
Paget's disease. The process proceeds by extension into the discharg- 
ing tubules and penetrates the gland structure. 

Medullary carcinoma, or soft cancer, is characterized by its softness 
and the abundance of liquid (cancer-juice). It grows rapidly and soon 




Fig. 405. — Ulcerated carcinoma of the breast. 



invades a large part of the gland, and attaches itself to the skin, which 
may finally be broken, exposing an ulcerated surface (Fig. 405). Actual 
inflammatory changes terminating in suppuration are not infrequent. 
The nipple is not retracted. 

Scirrhous cancer is slower in growth, and is usually very hard; the 
skin is firmly attached to the tumor, and the nipple is usually retracted. 
On section the tumor is found to be of a firm, fibrous, and somewhat 
translucent character; extensions of the growth are seen radiating in 
various directions from the body of the tumor. Microscopically, the 
growth consists of fasciculated connective tissue, enclosing round or 
elongated collections of cancer-cells (see Fig. 89). 



DISEASES OF THE REPRODUCTIVE ORGANS 



835 



Simple carcinoma stands between the medullary and the scirrhous 
forms in point of hardness, as well as in point of malignancy. The 
three forms differ only in the relative amount of epithelial elements and 
fibrous tissue. 

Myxomatous, colloid, or gelatinous cancer is a rare form in which 
the interstitial connective tissue suffers mucoid change, and the epi- 
thelial cells of the cancer-acini undergo more or less fatty or excep- 
tionally mucoid degeneration (see Fig. 90). 

Adenocarcinoma presents the general type of malignant adenoma. 
It may be solid or cystic or cystopapillomatous. It grows rapidly, and 
may go over into the soft or hard types. 

Malignant papillomata of the ducts have been seen. These may 
become extensive and carcinomatous. Hemorrhage into the ducts or 
through the nipple is common from them. 

Results. — Cancer of the breast may extend directly to the subcu- 
taneous tissues and skin on the one hand, causing an indurated growth 
(cancer en cuirasse), or to the walls of the chest and pleura on the other 
hand. Metastasis frequently takes place through the lymphatics, the 
axillary glands, as a rule, presenting the first evidence of the extension 
of the growth. Secondary growths are often found in the pleura and 
bones. Malignancy varies directly with the softness of the tumors, 
the scirrhous form frequently having a comparatively benign character. 
Sometimes the increasing growth of connective tissue in this variety 
leads to practical cessation of the growth of the tumor. 

Mammary cancers are much more frequent in the female than in 
the male sex. They are commonly met with after the age of forty, 
and traumatic influences seem to bear some relation to their occur- 
rence. 

Cysts. — Repeated reference has been made to the retention cysts 
of the lactiferous tubules caused by compression or other forms of 
obstruction. The gland may present a few or many cystic cavities 
about the size of a pea, containing whitish or milky liquid. Occa- 
sionally the contents of the cysts are cheesy {atheromatous). Disten- 
tion of the acini of the glands in consequence of obstructions to the 
outflow of milk may lead to large cystic tumors containing milk (galacto- 
cele) . In the later stages the contents of such cysts may become thick- 
ened or caseous. 



CHAPTER IX 



DISEASES OF THE BONES 

Anatomy and Development. — Bone is a dense form of connective 
tissue, the cement substance being impregnated with lime-salts. It 
may be spongy or compact in character. On transverse section one sees 
certain oval openings, surrounded by concentric lamellae of a substance 
containing lime-salts. Each opening is the end of a so-called Haversian 
canal, which with the surrounding lamellae forms an Haversian system. 
The areas between the Haversian systems are filled with osseous tissue 
not arranged concentrically. Between the lamellae of bony tissue are 
seen irregularly oval spaces — lacunae — from which run branching canal- 
iculi. In preparations of fresh bone the lacunae are found to be occu- 
pied by the bone-cells, which are irregular and have branching projec- 
tions extending some distance into the canaliculi. In the center of 
the bones are found hollow spaces containing the bone-marrow. This 
is a vascular tissue, in the meshes of which are found large and small 
rounded cells resembling the lymphoid cells, red corpuscles, ordinary 
leukocytes, and some nucleated red corpuscles. A form of cell of particu- 
lar interest is the large multinucleated giant cell, or myeloplaque. The 
marrow extends in the form of projections into the substance of the 
bone and communicates Avith the Haversian canals. 

Surrounding the bone is the fibrous periosteum. This consists of a 
dense outer layer and a more cellular inner one, which is osteogenetic in 
function. 

Development. — The beginning of the change of the original cartilage 
into bone consists in the multiplication of the cartilage cells and their 
arrangement in longitudinal rows. They grow into cartilage corpuscles 
of considerable size, calcification at the same time occurring in the 
matrix between these cells. Simultaneously, vascular projections ex- 
tend inward from the perichondrium ; the cartilage cells and preliminary 
calcareous deposit are subsequently removed, primary marrow-spaces 
being thus formed. Bone-cells are deposited in the spaces between the 
original cartilaginous trabecular, and at once begin to cover themselves 
with bony deposits, the cartilaginous trabecular gradually diminishing 
by absorption. By these processes a spongy form of bone is developed. 
Subsequently the concentric calcareous lamellae of the Haversian sys- 
tems are deposited within the spaces, and the spongy bone is thus con- 
verted into the dense form. 

Disorders of Development 

Many congenital defects of development are observed, such as the 
appearance of supernumerary bones, the absence of certain bones, the 

836 



DISEASES OF THE BONES 



837 



failure of union between epiphyses and diaphyses, etc. These conditions 
are of little pathological interest. One condition of considerable interest 
(rachischisis) is considered on page 933. 

The most important developmental disease is rickets. 

Congenital rickets, or chondrodystrophia fetalis, or achondro- 
plasia, differs in some respects from the disease met with after birth. 
The extremities are short and thick, the ends of the bones enlarged, 
and the shafts bent. The hand is curiously like a trident by reason 
of wide separation of the second and third fingers. There is increase 
of the original cartilage and of the periosteum, with an arrest of develop- 
ment of the bones. Subperiosteal bone formation is about normal, 
but epiphyseal growth is imperfect and the bones do not develop to 
their normal length. The cause is obscure, but the condition seems 
hereditary. The disease is essentially one of disproportionate or irreg- 
ular ossification of already mapped out cartilaginous parts. It begins 
early in fetal life, probably in the second month. The thyroid shows 
overgrowth of alveolar epithelium and connective tissue, the former 
surrounding the latter, with the formation of separated islands of acini. 

Closely related to the above is osteogenesis imperfecta, which, as its 
name implies, is an ossification short of completeness. The charac- 
teristic is to be found in the skull, where only small plates of bone are 
laid down, and these fail to unite to form the large flat bones. This 
may be a hereditary condition. It probably is due to delayed action 
of the periosteum, so that the shafts of long bones are imperfect and 
multiple fractures are common. Fragillitas ossium, or generalization 
of this, is discussed on page 848. 

The effect of all these malformations is to render adjacent parts 
liable to damage and to favor fracture of the bones themselves. 

RICKETS 

Definition. — Rickets, or rachitis, is a constitutional disorder, at- 
tended with abnormal developmental processes in the bones, of which 
active proliferation of the cellular elements and lack of normal calcifica- 
tion are the most important. 

Etiology. — The causes of rickets are still very obscure. The dis- 
ease is in some way connected with improper nourishment, though 
there is probably also an inherited disposition, or a constitutional con- 
dition expressing itself chiefly in an inability of the primary cartilage 
to absorb calcium salts and ossify normally. It has been sought to 
establish a connection between rickets and syphilis, but any such rela- 
tion is doubtful. Various chemical theories have been offered in ex- 
planation, a very ably defended one being that in some way calcium 
is eliminated in excess instead of being absorbed; the normal or very 
slightly reduced alkalinity of the blood in rickets speaks rather against 
this assumption. Formerly, it was supposed that the presence in the 
digestive tract of. lactic acid in excess prevented the proper absorption 
of calcium; this theory, however, is generally abandoned. It does not 



838 



A TEXT-BOOK OF PATHOLOGY 



seem that reduced calcium intake causes the disease, because experi- 
ments with low calcium diet do not produce rickets in young animals. 
Ribbert now asserts that the cause is toxic, the poison producing degen- 
erations in the cartilage-cells. The disease occurs in infants during the 
first year of life, and continues during the second and third years, after 
which the active manifestations subside. 

Pathological Anatomy. — Rickets leads to various deformities, 
principally situated in the long bones and skull. The epiphyses, as 
those of the wrist, ankle, etc., are swollen, and in more advanced stages 
the shafts of the long bones may be variously distorted. 

Sharp bends (infractions) may be observed in the long bones, and 
complete fractures may occur. The alteration of the skull is charac- 
teristic. The head is large and square in shape, the forehead prominent, 
and the fontanels remain open a long time. Osteophytes may form, 
and not rarely areas are found in the temporal or other bones in which 
the mineral substance is deficient or almost completely wanting (cranio- 
tabes), the spaces being filled by a parchment-like membrane. Deformi- 
ties of the chest are frequent, the chicken-breasted condition being the 
most marked. In the beginning of the disease slight enlargement of the 



Fig. 406. — Rachitic enlargement of the end of a rib (modified from Bollinger). 

ends of the ribs at the junction with the costal cartilages, causing the 
beaded appearance called the "rachitic rosary," is observed (Fig. 406). 
Various distortions of the spinal column, flattening of the pelvis, and 
other deformities may be met with in marked cases. 

The minute changes of rickets consist in a form of abnormal develop- 
ment, in which calcareous deposition does not progress in the normal 
manner, but is replaced by proliferation of the cellular elements. In 
consequence of this the bone presents irregular areas of partial calcifica- 
tion lying between portions made up of greatly proliferated and en- 
larged cartilage cells. Between the epiphysis and diaphysis of long 
bones there is a wide irregular bluish zone of imperfectly ossifying 
cartilage richly supplied with blood-vessels. Projections from the mar- 
row and periosteum extend deeply and visibly into the body of the bone, 
which is thus composed for the most part of osteoid instead of osseous 
tissue. The marrow-spaces are irregular and excessive in size. These 
changes in the bone are marked at the epiphyseal extremities, and thus 
lead to the visible enlargements. It is thus seen that the process in 
rickets is failure of development of the normal structure, rather than 
absorption of existing bone. The original calcareous deposit around 
the cartilage cells is largely or completely absorbed, as in normal bone- 




DISEASES OF THE BONES 



839 



formation, and often even more rapidly. The subsequent deposit of 
calcareous bone does not form, but in place of it there occurs a rapid 
proliferation of cartilaginous and other cells. 

When, however, the progression of the disease is stopped, calcifica- 
tion occurs as usual, although there is a tendency to extreme hardness 
of the bone, small Haversian systems, and excessive periosteal bone. 

Associated Conditions. — The changes in the bones do not con- 
stitute the entire pathology of rickets. There are frequently gastro- 
intestinal disorders, such as catarrhal inflammations of the mucous 
membrane. Proliferative changes are met with in the spleen and liver, 
leading to fibrous overgrowth and enlargement, and the blood is more 
or less profoundly altered. Decrease in the number of red corpuscles 
and leukocytosis are the conspicuous features. Nucleated red corpuscles 
may be found in more or less abundance, according to the grade of 
anemia, and the leukocytosis involves a special increase of mononuclear 
elements; a myelocytes may be present. 

REGENERATION OF BONE 

Regeneration of bone occurs most typically in the healing of frac- 
tures, and also as a part of various pathological processes in which a 
certain amount of destruction of bony tissue has taken place. Hyper- 
trophy may be included in the same group of affections. 

Fractures. — Definition. — Fractures are breaches in the continuity 
of bone which occur in consequence of direct force or of muscular con- 
tractions. The bone may be broken in various directions, the line of 
fracture being straight or irregular, directly transverse to the long 
axis of the bone, or oblique. The bone may be broken into a number of 
splinters (comminuted fracture), or the fracture may be a single one. 
There is always more or less injury to the soft parts immediately sur- 
rounding the bone, and sometimes extensive injury causes communica- 
tion between the outer surface and the seat of fracture through flesh 
wounds (compound fracture). 

Repair of Fractures. — The process of repair is much the same as 
the process in the original formation of bone. Immediately after the 
fracture there is more or less hemorrhagic extravasation within the 
marrow and around the broken ends of the bone. Within a few days 
cellular infiltration, with congestion and edematous swelling of the 
periosteum and marrow, as well as of the bones, may be noted. Pro- 
liferative changes then take place in the same situations and new blood- 
vessels are formed. The adult bone-cells do not regenerate bone, this 
process devolving upon the osteoblasts of the periosteum and marrow. 
They multiply and arrange themselves and their intercellular substance 
in a form similar to that of bone into which first cartilaginous, then osse- 
ous, matter is deposited. The condition of this tissue varies greatly in 
different cases; sometimes it is quite fibrous, in other cases almost purely 
cartilaginous. Gradually it is converted into bone by the regular 
processes of bone-formation. At this stage the seat of fracture is 



840 



A TEXT-BOOK OF PATHOLOGY 



occupied by a deposit of soft, bony material of considerable bulk, 
which causes a local thickening of the bone. Finally the excess (tem- 
porary callus) is removed by absorption, the parts in the direct line of 
the bone upon which the strain naturally falls become thickened (defini- 
tive or permanent callus), and other parts are absorbed. 

The original deposit of osteoid or chondroid material at the seat of 
fracture is termed callus (Fig. 407). Part of this is deposited on the 
exterior (periosteal callus), and is derived from the periosteum; part is 
within the marrow cavity {myelogenous callus); and a third part is 




Fig. 407. — Fracture of the femur, show- 
ing malposition of the ends of the bone and 
abundant callus (modified from Bollinger). 




Fig. 408. — Fracture of humerus; sec- 
tion through the bone, showing the repair 
of the fracture (modified from Bollinger). 



sometimes seen between the ends of the bone (intermediary callus). 
The last is produced by the periosteum. 

The healing of fractures under the most favorable circumstances — 
that is, in cases in which the fragments of bone are restored to their 
proper position — is accomplished with but little disturbance of the 
normal relations. The seat of fracture may be permanently thickened, 
and there is always some shortening of the affected bone, when the 
fragments are not placed in proper position, or angular deformities may 
result with considerable thickening from deposit of bony material 
between the fragments (Fig. 408). 

When the fragments are not kept in apposition, or when the general 
condition of the patient is unsatisfactory, the union of the fragments 



DISEASES OF THE BONES 



841 



may be prevented and "ununited fractures" result. The ends of the 
fragments in these cases become rounded by absorption of the sharp 
edges, forming false joints (pseudarthroses) . 

When ossification is imperfect fibrous union takes place. 

Hypertrophy 

Local or general hypertrophy of bone may be found. Local hyper- 
trophies may occur in consequence of increased strain upon certain 
parts of a bone, either directly or through the muscles. In muscular 
individuals hypertrophy of this kind is frequently seen at points of 
attachment of the muscles. In cases of injury or incapacity of one of 
the limbs the other may show hypertrophy. 

Giant growth of certain bones, or of the entire skeleton, may be 
observed. Local hypertrophy of this kind, dating from childhood, is 
especially common in the upper extremities, and is frequently unilateral. 
It may be observed as a bilateral condition in the fingers. Complete 
giant growth usually begins about the age of puberty. The individual, 
previously developed as others, begins to grow abnormally until an ex- 
cessive size is reached. The bones are not only very large, but often 
markedly thickened and irregular. 1 

Acromegaly is an allied condition in which giant growth of the 
hands and feet, forearms and legs, and parts of the face, notably the 
lower jaw and parts of the cranium, is observed. A certain amount of 
hyperplasia of the soft tissues in the affected region accompanies this 
change. Hyperplastic conditions, tumors, and other diseases of the 
hypophysis cerebri, especially of the anterior lobe, have been met with 
in a considerable proportion of the cases. In some of the skeletons of 
giants investigated with regard to this point enlargement of the sella 
turcica has been found, and this evidences the occurrence of enlargement 
of the pituitary body in some, at least, of such persons. The exact rela- 
tion between pituitary disease and bony hypertrophies remains obscure. 
(See Hypophysis.) 

CIRCULATORY DISTURBANCES 

Hyperemia is normal during the development of bone, or may 
accompany inflammatory disturbances of the neighboring parts. The 
marrow becomes more or less light- or dark-red in color, and the perios- 
teal vessels may be injected. The entire bone may have a pink or reddish 
color. 

Thrombosis may occur in the blood-vessels of the marrow, giving 
rise to areas of degeneration or myelitis, or in the cancellated tissue at 
the ends of long bones, in which case it may be of importance in the 
production of osteomyelitis or arthritis if the thrombus be infective. 

Hemorrhage beneath the periosteum and in the marrow is com- 
paratively common. It may result from traumatic causes or from scor- 
butic or purpuric conditions, as well as from inflammatory affections 



842 



A TEXT-BOOK OF PATHOLOGY 



of the parts involved. Considerable subperiosteal hemorrhages are 
found in cases of infantile scurvy. The separation of the periosteum 
from the bone may lead to necrosis of the superficial layers of the bone. 
A similar accumulation of blood beneath the periosteum is that found 
over the bones of the skull in the newborn — the cephalohematoma. 
This results from the traumatism of labor. Large accumulations of 
blood of this nature may be absorbed or may undergo suppuration. 

Hemorrhage into the substance of bone may accompany other dis- 
eases affecting it, such as caries, tumors, and the like. . 

INFLAMMATIONS 
Periostitis 

Definition. — Periostitis, or inflammation of the periosteum, may 
be of various forms, and may lead to different results. Sometimes the 
evidences of inflammation are very apparent; in other cases the disease 
appears in the form of a chronic productive process, leading to over- 
growth. 

Etiology. — Periostitis may be the result of traumatism, with or 
without the establishment of a communicating wound. In the latter 
case the injury provides an area of lessened resistance, which may 
subsequently become infected. In the former case the infection is direct, 
coming from the outside. Hematogenous infection without local injury 
is frequently observed. Infective periostitis may result from extension 
of an inflammation situated near the bones or from osteomyelitis. In 
all forms of bone disease more or less local periostitis occurs as a com- 
plication. In some cases the etiology is obscure, as in the periostitis 
which occurs during pregnancy and leads to the formation of osteo- 
phytes. 

Pathological Anatomy. — We may distinguish simple, suppurative, 
and ossifying periostitis; the simple may pass into the severer grades. 

Simple Periostitis. — The membrane becomes swollen, red, and 
sometimes infiltrated with blood. Microscopically, there are round-cell 
infiltration and proliferation of the periosteal tissue. If the process 
has been extensive and the irritation long continued, a termination in 
fibroid thickening may be observed. This is not unusual in cases of 
fractures. 

Purulent Periostitis. — The disease may be circumscribed or diffuse. 
There are marked swelling and cellular infiltration, particularly in the 
deeper layers, and abscess-formation results. Separation of the perios- 
teum from the bone ensues, because of the tendency of the pus to dissect 
between the bone and its covering; this may lead to local interruption 
of the circulation between the periosteum and the bone, and consequent 
superficial necrosis of the bone with exfoliation results. In the diffuse 
form of periostitis widespread areas of the periosteum may be quickly 
involved and rapid destruction takes place. In these cases a consider- 
able inflammation of the surrounding tissues is customary. In all in- 



DISEASES OF THE BONES 



843 



stances there is a tendency to burrowing of pus toward the surface, and 
its eventual discharge. The retention of necrotic portions of the bone 
may lead to continued suppuration, but with removal of the dead 
portions healing usually occurs. Ostitis and osteomyelitis are very 
frequent results of periostitis; on the other hand, they may be in certain 
cases the original cause. 

Ossifying periostitis leads to the formation of bony excrescences, 
exostoses, or osteophytes. There is first a proliferation of the osteogen- 
etic layer of the periosteum, then partial ossification, and finally complete 
bone-formation with firm attachment to the underlying bone. The 
osteogenesis is essentially the same, but the periosteal bone-depositing 
cells are working in a tissue the seat of productive fibrosis, so that the 
calcium salts are not laid down in an orderly manner along the surface 
of the bone. These changes may be circumscribed or diffuse, and cause 
irregular elevations or general thickening of the bone. The exudate 
may be merely fibrous tissue or a soft albuminoid material, usually 
leading to periosteal thickening, but occasionally involving the bone or 
the marrow. Occasionally the surrounding connective tissues are 
implicated (parostitis) . Ossifying periostitis may occur in the vicinity 
of joints affected with chronic arthritis. It may occur as a result of dis- 
eases of bones attended with considerable destruction, such as tumors, 
tuberculosis, etc. Occasionally the causes are entirely obscure. An 
interesting form is that which occurs in the bones of the hands and 
feet, forearms, and legs in tuberculosis of the lungs and empyema, or 
more rarely in other diseases; to this the term hypertrophic osteo-arthrop- 
athy has been applied. This is a form of osteoperiostitis of ossifying 
type, and it seems to be due to the action of circulating toxins developed 
in the diseases with which it is associated, or to chronic passive conges- 
tion. Perhaps both factors are important. 

Associated Conditions and Results. — The conditions met with 
in the adjacent bones and other parts have been referred to. General 
infection and intoxication may follow upon the suppurative cases, and 
death may then occur from septicopyemia. Permanent thickening of 
the bone may result in any case, or resolution may be practically com- 
plete. • 

Osteomyelitis and Ostitis 

Definition. — Acute osteomyelitis and ostitis are usually combined, 
and occur as an inflammatory condition affecting the marrow and its 
extensions into the communicating canals of the bone. The lamellar 
substance of the bone is only secondarily involved. 

Etiology. — Osteomyelitis is an infective disease resulting from 
hematogenous infection in the course of various diseases, from local 
infections in cases of traumatism (fracture, amputation), or from peri- 
ostitis. Various micro-organisms, including staphylococci, streptococci, 
typhoid bacilli, and the Bacillus coli communis, have been discovered. 
The so-called primary or idiopathic cases are frequently secondary to a 
boil or an angina, and occur commonly in adolescents. 



844 



A TEXT-BOOK OF PATHOLOGY 



Pathological Anatomy. — The marrow first becomes red and edem- 
atous, then cellular infiltration and proliferation are superadded, and 
finally collections of pus or diffuse purulent transformation follow. Large 
areas of necrosis appear in the marrow and in spongy bone because of the 
cellular infiltration and vascular thrombosis. The surrounding bone is in- 
volved, becoming more or less infiltrated, soft- 
ening, and not rarely undergoing necrosis (Fig. 
409) . Small or large sequestra may be formed, 
or the bone may necrose completely. Perios- 
titis is generally associated by extension through 
the Haversian system, and this layer is lifted 
from the bone, which thus deprived of nourish- 
ment from without undergoes rapid necrosis. 
The tissues around the bone are usually infiltra- 
ted ,and suffer suppurative or necrotic changes. 
The process extends to the spongy ends, and to 
the joint surfaces in severe cases, and the sup- 
puration cuts off the circulation. From here 
metastatic processes can arise from infected 
thrombi. Hypertrophic changes may occur in 
the periosteum and superficial layers of bone, 
causing a bony encasement (involucrum) of 
central sequestra. In such instances a suppu- 
rating sinus, extending from the bone to the 
surface, usually remains. 

The rapidly developing cases of youth 
commonly begin as a epiphysitis, probably the 
result of infective embolic thrombosis; in ful- 
minating cases there may be a general gangre- 
nous myelitis. 

Associated Conditions. — Implication of 
the neighboring parts is habitual — deep-seated 
abscesses, arthritis, etc. General infection is 
usually the final result, and commonly leads 
to a fatal end. Marked changes in the blood 
have been observed — leukocytosis, with large proportions of large 
mononuclear cells, myelocytes. 

Chronic Ostitis 

Chronic inflammatory processes are more apt to involve the bone 
than the marrow, though the beginning of the disease may be fre- 
quently in the latter situation. It may be suppurative, degenerative, 
or hypertrophic in character. 

Etiology. — Chronic ostitis may follow osteomyelitis and necrosis, 
necrotic sequestra keeping up a constant irritation. In these cases 
the disease is primarily infective. The chronic inflammations of bone 
due to tuberculosis and syphilis have special characters, which will be 
described below. In many cases the cause of chronic ostitis is obscure,, 




Fig. 409. — Necrosis of 
femur, the result of acute 
osteomyelitis (Warren) . 



DISEASES OF THE BONES 



845 



though probably circulating toxic substances are the specific factors. 
Direct traumatism, periostitis, or other inflammatory diseases sur- 
rounding the bone may be the immediate causes. 

Pathological Anatomy. — In the necrotic and suppurative form, 
following osteomyelitis, there is more or less softening of the bony sub- 
stance by absorption of the calcareous matter, and at the same time 
proliferation, in the form of granulation tissue, of the cellular elements 
of the marrow and its prolongations within the Haversian channels. 
Localized abscesses may be formed, or infiltration of pus in various 
directions with increasing necrosis of the intervening bone may occur. 

The degenerative form of ostitis is a variety in which the calcareous 
matter is absorbed, and the bone thus rendered more soft and porous. 
The term inflammatory osteoporosis is applied to this. In the process of 
absorption there are formed upon the outer and inner surfaces of the 
bone, or within its substance, areas of erosion, hollow spaces or indenta- 
tions, showing bone-corpuscles and giant cells lying upon the eroded 
bony tissue. These depressions are the so-called Howship's lacunae. 
The giant cells, which are active in the absorptive process, are termed 
osteoclasts, and are anatomically identical with the osteoblasts or osteo- 
plaxes of developing bone. It may be that the leukocytes of the bur- 
rowing pus are also able to produce absorption of bone structures. 
Simultaneously with this absorption of the lamellae of bone there is 
proliferation of the marrow substance in the eroded areas, and at the 
same time there may be increased vascularization of this intervening 
tissue. Perforations are frequently established through the lamella? 
by the penetration of new-formed blood-vessels, so that neighboring 
excavated areas communicate. This form of inflammation of the bone 
is frequent in the neighborhood of necrotic areas or osteomyelitic collec- 
tions of pus, and plays a part in the pathological processes of osteomalacia 
and other bone diseases. It is rarely an independent condition. 

The hypertrophic form of chronic inflammation leads to increased 
density of the bone, to which the term condensing ostitis, or osteosclerosis, 
is applicable. It may occur as a reactive process surrounding areas of 
osteoporosis or other local diseases of the bone, or in association with 
ossifying periostitis. Occasionally, it occurs in certain bones or parts of 
bones without local or well-ascertained general causes. Such cases are 
met with in syphilitic persons. The anatomical changes consist in the 
deposition of increased quantities of bony tissue by the same processes 
as are operative in normal bone-formation. It is, therefore, a process 
in which the reparative forces have gained the field, a reverse of rarefy- 
ing ostitis. The lamella? become wide, and the vascular spaces are 
encroached upon and sometimes wholly replaced by bony tissue; the 
osseous tissue which is laid down is very compact and the bone channels 
are narrow. 

The disease designated as leontiasis ossium is a form of osteosclerosis 
affecting the bones of the head and face, and causing irregular thicken- 
ing and enlargement of these bones. The cause of this condition is 
obscure. 



846 



A TEXT-BOOK OF PATHOLOGY 



Ostitis Deformans 

Ostitis deformans is a condition which affects the skull, vertebra, 
and certain long bones, causing enlargement of the affected parts and, 
on account of the elasticity of the diseased bony parts, great deformity. 
Fractures do not occur. Pathologically there is absorption of the com- 
pact bone, with confluence of the Haversian canals and new formation 
of osteoid tissue and fibrous tissue throughout the diseased structures. 
There is a deforming ossifying periostitis accompanying the internal 
absorption. The medullary cavities of the long bones are filled with 
vascular connective tissue and abundant fat-cells, and sometimes cysts 
containing gelatinous material are observed. Giant-celled sarcoma may 
occupy the medulla. The etiology of the disease is obscure, but some 
form of trophic disturbance undoubtedly plays a part in the causation. 

DEGENERATIVE CONDITIONS 

Caries 

Caries is a term applied to the molecular destruction of bone, 
corresponding to ulceration of the soft parts. It may be associated 
with osteomyelitis, or with necrosis due to traumatism or various 
infective conditions. The changes consist in progressive softening and 
crumbling of the bone, with eventual destruction of more or less con- 
siderable areas. Caries is especially frequent as a part of tuberculosis 
of the bones, and will be described in connection with that disease. 

Necrosis 

Definition. — Necrosis is term applied to the death of a small or 
large portion of bone in mass. 

Etiology. — Among the causes are the various acute or chronic 
diseases of the periosteum, bone-marrow, and adjacent bone. In cases 
of purulent periostitis the separation of the periosteum from the under- 
lying bone leads to interruption of blood-supply and superficial necrosis. 
Similar results occur in cases of osteomyelitis. Necrosis of the bone 
may also occur in consequence of embolic obstruction of the blood- 
vessels. 

Pathological Anatomy. — Necrosis may be partial or total, and 
may occur in the center of the bone or at the periphery. The dead 
portion of the bone, termed sequestrum, presents itself as an irregular, 
more or less eroded fragment, almost completely or completely sepa- 
rated from the remaining structure. The separation occurs by the 
process of demarcation, as in necrosis of the soft parts. This line con- 
sists of an area of absorption of the calcareous matter and proliferation 
of the cellular elements. The necrotic portion, or sequestrum, acts as a 
foreign body, and by its continued irritation keeps up a suppurative 
inflammation of the surrounding tissues. Fistulous communication 



DISEASES OF THE BONES 



847 



with the exterior is usually observed. If the sequestrum is peripheral 
and has been discharged, the periosteum or the bone may replace the 
lost tissue by regeneration. If the fragment is large or centrally placed, 
discharge is impossible and suppurative inflammation continues, some- 
times for years. Bony tissue usually responds to the presence of a seques- 
trum by the formation of sclerosing ostitis and periostitis, and consider- 
able hyperplastic material may be deposited over and around the 
sequestrum, and thus irregular thickening of the bone may be produced. 
At times, however, the continued irritation and suppuration may lead to 
complete destruction of all the bony tissue in the neighborhood. 

A peculiar form of necrosis is that occurring in consequence of 
chronic phosphorus-poisoning. It is met with in persons engaged in the 
manufacture of phosphorus matches, and affects the maxillary bone. 
The existence of carious teeth aids in the development of this form of 
necrosis, probably by admitting micro-organisms which infect the bone 
already altered by the poison. The process begins in the periosteal and 
subperiosteal portions of the bone, and ends in more or less complete 
necrosis. 

Associated Conditions. — Long-standing necrosis causes great 
deterioration of the general health, particularly in cases in which sup- 
purating sinuses are formed. Systemic infections may follow and 
amyloid degeneration of various organs may occur. 

HYPOPLASIA AND ATROPHY 

Hypoplasia, or the lack of development of bones, may occur as a 
local or general condition. Local hypoplasia may be due to injuries or 
diseases which render a part of the body useless. General hypoplasia is 
found in cretins and dwarfs. 

True atrophy of the bones may involve an entire bone or only 
portions of it. General atrophy of the whole or of parts of a bone occurs 
as a result of inactivity or want of use, as in cases of palsy, chronic 
rheumatism, and the like. The process is one of greater activity of the 
osteoclasts than of the osteoblasts. It may begin in the marrow canal 
and proceed outward, eccentric atrophy, or beneath the periosteum, 
concentric atrophy. The Haversian canals are widened and a condi- 
tion of osteoporosis arises. The implication of certain parts of the 
nervous system (trophic centers) is particularly important, as the 
atrophy resulting in such cases is much more extensive than that 
occurring in cases of similar inactivity from other causes. 

Partial or local atrophy of the bone may be due to pressure by 
aneurysms, tumors, and the like. In these cases there is gradual absorp- 
tion of bony substance, and the process is really one of inflammatory 
osteoporosis. 

General Atrophy. — Absorption of the bony substance, with 
resulting osteoporosis, may occur in marasmic individuals, particularly 
in seniles. In these cases it is held by most authorities that the path- 
ological condition is dependent upon the failure of replacement of bone 



848 



A TEXT-BOOK OF PATHOLOGY 



to make up for the normal absorption constantly taking place. In 
these cases the bone becomes extremely fragile from the increase of its 
marrow-spaces and its general porosity. A condition of excessive fragil- 
ity is termed fragilitas ossiuvi, or osteopsathyrosis . Occasionally this 
condition of fragility is met with as an idiopathic disease, without 
definitely discoverable causation and without evident disease of the 
bones. Such cases have been found to occur in certain families through 
several generations. 

Osteomalacia 

Definition. — This disease is probably a constitutional condition 
leading to absorption of the bone-salts and to other changes in the bone, 
which cause extreme flexibility. 

Etiology. — The causes of osteomalacia are still obscure. It is a 
disease occurring with especial frequency in puerperal women, but it 
may occur in men and in non-puerperal women. A number of theories 
have been offered to explain the disease, but none of them has been 
established. In some respects it seems not unlikely that it is a tropho- 
neurosis, based upon the fact that the removal of the ovary brings 
benefit in some cases. It is also thought that adrenal insufficiency plays 
a part, and treatment with adrenal extract has a good effect in some cases. 
Most authorities look upon it in pregnancy as an exaggerated natural 
process of giving up inorganic salts to the fetus. An excess of earthy 
material is excreted in osteomalacia. There is loss of calcium and increase 
of sulphur and magnesium in the bones during active osteomalacia. It 
is particularly frequent in certain regions (endemic), while in others it 
occurs very rarely (sporadic). 

Pathological Anatomy. — The changes in the bone lead to various 
deformities and changes of appearance. Distortions, bends, and even 
fractures are observed in the long bones, and deformities due to abnormal 
curvatures of the spine are not infrequent. The shaft of the long bones 
may become of paper thickness. The pelvis shows peculiar changes 
which may prove very troublesome during labor. The characteristic 
change is a beaked condition, due to displacement forward of the pubes 
and a lateral indentation. This gives a triangular form to the outlet 
of the pelvis or superior strait. The bone-marrow is often quite red, and 
the periosteum in the neighborhood of bends or fractures may be thick- 
ened by cellular proliferation. The minute structure of the bone in 
osteomalacia shows a more or less pronounced absorption of calcareous 
matter, but the normal lamellar arrangement of the bone may be 
preserved. With the abnormal bone absorption there is a tendency to 
considerable deposit of osteoid material, but calcification of this sub- 
stance is never completed. In the region of bends and fractures osteoid 
tissue of irregular structure, with bony corpuscles of considerable size, 
may be observed ; while in other situations the regular lamellar arrange- 
ment and the ordinary small-sized bone-corpuscles are seen. Irregular 
areas of homogeneous or granular appearance may be interspersed within 
the normal osseous tissues. The line of demarcation between such 



DISEASES OF THE BONES 



849 



abnormal non-calcareous portions and the unaltered bone may be either 
sharply drawn or diffuse. 

Associated Conditions. — Patients suffering from osteomalacia 
are usually reduced or cachectic, and frequently perish with terminal 
pneumonia. Some cases end in recovery by restitution of the bone. 
It has been claimed that there is evidence in all cases of puerperal women 
of some bony absorption, and osteomalacia, therefore, would seem to be 
but an exaggeration of normal conditions. Normally, the slight bony 
changes are corrected after the puerperal period is passed. 

INFECTIOUS DISEASES 
Tuberculosis 

Tuberculosis may occur in bones in several forms. Miliary tubercles 
may be found in the bone-marrow in the course of general miliary 
tuberculosis, and local tuberculous disease of the periosteum may be 
met with. The most frequent and most important form of tubercu- 
losis is tuberculous ostitis with caries. 

Etiology. — The involvement of the bones is nearly always second- 
ary, the first manifestations of tuberculosis occurring in other struc- 
tures, notably the lymphatic glands and the lungs. The original focus 
of disease is, however, frequently small, and may remain quiescent while 
the lesion in the bones advances. The disease of the bones may be due to 
direct extension or to hematogenous infection. Not rarely the joints 
are first involved and the neighboring bones only secondarily; indeed, 
it has been said that tuberculosis first noticeably affecting the epiphyses 
spreads from lesions in the synovia of adjacent joints. The epiphysis 
of a long bone and the cancellated tissue of flat and irregular bones are 
much more easily affected with tuberculosis than the marrow of long 
bones. Doubtless, both the epiphysis and metaphysis may be infected 
from joint cartilages. Fraser suggests that the settling point of the 
tubercle bacillus may be an endarteritis due to tuberculous toxemia. 

Traumatic influences are of importance in determining the situation 
of hematogenous tuberculosis. The traumatism causes circulatory 
disturbances in the bone, and thus produces a suitable soil for the bacilli 
to find lodgement. Bone tuberculosis is most frequent in early life; it 
may actually begin in idero. 

Pathological Anatomy. — Tuberculosis attacks by preference the 
outer layers of the marrow, the spongy bony tissue, and the periosteum. 
In the last there is usually proliferative change with caseation, caries 
of the underlying bony layers, and fibrosis. The tuberculous lesion of 
bone first presents itself as an area of grayish color, with congestive 
reddening of the parts around and intense injection of the bone-marrow 
in its vicinity. Subsequently there are rapid cheesy change and more 
or less softening of the area of inflammation. Microscopically, tubercles 
in various stages of degeneration are discovered, and in addition areas 
of diffuse tuberculous granulation tissue and caseous degeneration 

54 



850 



A TEXT-BOOK OF PATHOLOGY 



(Fig. 410). The marrow about the tubercle is at first the seat of diffuse 
hyperplasia which gives away to lymph-cell infiltration, and this is in 
turn followed by fatty and fibrous tissue overgrowth. Lamellar changes 
are at first in the form of rarefying ostitis with caseous infiltration, 
about which extension occurs and new foci are established. The entire 
diseased area may be separated from the uninvolved bone as a seques- 
trum, but more frequently there is gradual carious softening, with 
formation of semifluid, cheesy material containing gritty particles of 
bone or calcareous matter ("bone sand"). Complete softening leads to 
the formation of a "tuberculous abscess" (Fig. 411). In these cases 
a more or less irregular cavity is formed within the bone, the wall of the 
cavity being covered with a pyogenic membrane developed from the 
marrow and its extensions into the Haversian canals. The contents of 




Fig. 410. — Tuberculous caries of one of the bones of the foot: a, Bony trabecula; b, 
tubercle with caseous center; c, caseation in a focus of tuberculous tissue; d, giant cells 
in tubercles; e, osteoclasts; /, fatty marrow (Kaufmann). 

the abscess are puriform or cheesy. The process tends to extend to 
neighboring parts, particularly to the joints. When the abscess has 
penetrated the encasing bone it may spread within the soft parts, thus 
forming large tuberculous abscesses (so-called cold abscesses). 

The periosteum reacts to the lesions within the bone by the forma- 
tion of a productive periostitis, the new formation being either densely 
packed lamellae or similar to spongy bone. An osteoporosis may appear 
beneath the periosteum when tubercles form on the under surface of 
that tissue. 

Reactive changes may occur locally, and more or less restitution may 
take place. Complete encapsulation of a small focus may occur by the 
formation of a surrounding zone of granulation tissue and cicatrization, 
or by new formation of bone occurring after the activity of the tuber- 



DISEASES OF THE BONES 



851 



culous process has been arrested. When adjacent portions of articulat- 
ing bones are involved the integrity of the articulation is disturbed, 
and subsequently ankylosis may be established by the formation of 
exostoses and their union. The spread of the lesions toward joint sur- 
face is favored by the predilection of the tuberculous 
process for the spongy bone at the epiphysis, where 
it is apt to cause infarct-like anemic areas by arteritis 
or phlebitis. Obliterating endarteritis is commonly 
seen near the lesions. 

Some fairly distinct forms of bone-tuberculosis may 
be recognized pathologically, depending upon different 
combinations of the histological features above out- 
lined. A large caseous tubercle may become encysted 
by fibrous tissue, but retain a sequestrum. There may 
be at times a diffuse puriform exudate without definite 
tubercles, but with rapidly advancing osteoporosis; 
this may possibly be due to mixed infection. There are 
also forms rather slow in their progress, the atrophic 
and hypertrophy, in which osteoporosis and osteoscle- 
rosis are respectively the predominating features. 

Seats and Associated Conditions. — Among 
the bones more frequently affected are the vertebrae, 
the long bones, particularly the femur, and parts of 
the skull. In the vertebra? the bodies are generally 
affected, and angulation or distortion of the spine 
results (Pott's disease). The cold abscesses formed 
in these cases may burrow considerable distances, 
pointing far below the place of origin. Those spring- 
ing from the cervical vertebra? may point beneath 
the mucous membrane of the pharynx or esophagus, 
or anteriorly in the neck above the clavicle or 
shoulder. The abscesses formed in tuberculous 
caries of the dorsal vertebra? may point under Pou- 
part's ligament. Tuberculous disease of the petrous 
portion of the temporal bone is not infrequent fol- 
lowing tuberculous disease of the ear; it is important 
as a possible cause of tuberculous meningitis. Tu- 
berculosis of the head of the femur and of the hip- 
joint is one of the most frequent forms of surgical 
disease in children. The phalanges are sometimes 
involved in early childhood by a curious form of tuberculosis, in which 
the shaft of the bone increases in size by gradual absorption and tuber- 
culous softening within and deposition of new bone from the periosteum 
without. 

Syphilis 

Syphilitic disease of bones may appear in various forms. Allusion 
has already been made to the condensation of the bones, or osteosclerosis, 



Fig. 411.— Tuber- 
culous "abscess" in 
the lower end of the 
humerus (modified 
from Bollinger). 



852 



A TEXT-BOOK OF PATHOLOGY 



in this disease. Syphilis may also occur in the periosteum as a nodular 
periostitis, or in the substance of the bone in the form of degenerating 
gummata. Congenital syphilis gives rise to certain peculiar alterations. 

Etiology. — Syphilitic changes in bone are confined almost exclu- 
sively to the tertiary period. They may occur without other luetic 
disease, or as concomitants of hepatic, splenic, or other visceral disorders. 
The disease of the bones is frequently determined by local injuries; 
especially is this true of the periosteal forms. 

Pathological Anatomy. — Syphilitic periostitis is very common 
upon the shin-bone, less- frequent in the periosteum of other long bones. 
There is, first, slight swelling of the periosteum, due to multiplication of 
the cells. Subsequently, this cellular mass undergoes cheesy or mucous 
degeneration, and the mass presents the appearance of a small gumma. 
Superficial erosion, or even necrosis, of the bone may take place, and 
discharge of the contents may occur. Following this, hypertrophic 
processes in the bone and adjacent periosteum lead to the formation 
of bony nodes. These nodes may, however, be formed without the occur- 
rence of softening and discharge from the periosteal lesion, the process 
in this case being one of simple ossifying periostitis. Gummata of the 
bones generally begin in the deeper layers of the periosteum, but tend 
to involve the bone more extensively than the form just described. 
The gummatous infiltration and proliferation occur along the blood- 
vessels of the periosteum and extend into the substance of the bone. 
Considerable areas may thus be implicated. The bone itself is ab- 
sorbed, or may undergo rapid caries or necrosis, with weakening of the 
bone, but with little tendency to sequester formation. Around the area 
of syphilitic change may occur a zone of reactive hyperplasia of the bone 
and periosteum. This may take the form of ossifying inflammation, 
giving rise to diffuse hardening of the shaft or of the layers directly under 
the periosteum, or hyperostoses may develop. The gummata themselves 
become cheesy or undergo mucoid degeneration, and eventually may 
discharge upon the surface. Syphilitic gummata are most frequent in 
the bones of the head, tibia, and sternum. 

Occasionally, gummata arise in the marrow of the bones instead of 
in the periosteum. 

Congenital Syphilis. — The bony changes of congenital syphilis are 
quite characteristic. The virus attacks the fetal cartilage, causing an 
irregular proliferation as a sort of granulation tissue and the deposit 
of bone salts without proper arrangement. The alterations occur at the 
junction of the epiphyses with the diaphyses of the long bones. Longi- 
tudinal section through these parts shows the line of junction as a bluish- 
white or yellowish-white irregular zone about 2 or 3 mm. in thickness 
(Plate 14) . In more advanced stages this line becomes thicker and more 
yellow. The epiphyses may be completely separated from the shaft. 
The minute changes consist in proliferation of the cartilage-cells and 
fatty degeneration, about which bone is laid out irregularly the 
spaces between the lamellse containing granulation tissue and atypical 
bone-cells. 



PLATE 14 




Epiphyseal junction in congenital syphilis; section stained with hematoxylin. 



DISEASES OF THE BONES 



853 



Associated Conditions. — Involvement of the neighboring parts 
is not infrequently seen in syphilitic diseases of the bones; thus there 
may be gummatous infiltration of the superficial tissues with syphilis 
of the bones of the extremities, while in the case of skull-bones extension 
inward may lead to involvement of the dura and brain. When the 
process occurs about the foramina of exit of nerves the sheaths of the 
latter may become involved. Gummata of the sternum sometimes lead 
to the formation of retrosternal collections of puriform material. 
Amyloid degeneration of various organs frequently follows bone- 
syphilis. 

Actinomycosis 

Actinomycosis attacks bones, most often those of the face and thorax. 
It occasions a rarefying, suppurative, or necrotizing complete osteitis, 
with involvement of adjacent tissues. There is little, if any, reactive 
limiting granulation tissue. 

Lepra 

Changes may occur in the bones in cases of mutilating leprosy, or 
more rarely in nervous lepra. Among these changes are ostitis and osteo- 
myelitis associated with new tissue resembling lepra nodules; consider- 
able destruction of the bones may be produced. 

TUMORS 

Exostoses are frequently met with in connection with definite 
disease of the bones and joints, or as more or less idiopathic outgrowths 
(see Fig. 55). They may be cartilaginous or fibrous in character, but 
subsequently may become osseous. They present themselves as flat, 
rounded elevations, or as more or less irregular outgrowths. Sometimes 
they are multiple and involve a number of bones of the skeleton. In 
such cases, particularly, heredity has been claimed as an important 
cause. 

Similar hypertrophic growths may appear within the marrow canal, 
especially in spongy bone, enostoses. 

Fibroma, lipoma, myxoma, and angioma may be mentioned 
among the true tumors as benign growths occasionally met with. They 
arise most frequently from the periosteum. 

Chondroma and osteoma are more common than these, and 
involve any part of the bone (see Figs. 53 and 56, pp. 177, 180). 

Sarcoma. — The most important of the primary tumors of bone 
is sarcoma. This may originate in the periosteum, bone-marrow, or the 
bone itself. It may be spindle-celled, or less frequently round-celled 
or alveolar. Sometimes it is melanotic. The giant-cell sarcoma, or 
osteosarcoma, is particularly important. It is most frequently met 
with in the lower jaw, beginning within the bone and causing a more 
or less rapid swelling. The tumor is surrounded by a shell of bone, 
which, however, sooner or later becomes perforated when the new 



854 



A TEXT-BOOK OF PATHOLOGY 



growth spreads to the neighboring parts (see Fig. 64). In all forms 
of sarcoma there is absorption of the bone substance in the vicinity. 
A form of sarcoma springing from the periosteum is described under 
the name of osteoid sarcoma. This tumor consists of fibromatous or 
round-celled sarcomatous tissue in which osteoid elements are irregu- 
larly embedded. More or less calcification and bone-formation are 
observed. The tumor may be quite soft or very hard; it tends to spread 
to the marrow cavity and absorb the shaft; it also extends to neighbor- 
ing soft parts and may give rise to metastasis. It is particularly fre- 
quent at the ends of the long bones (see p. 196). 

Sarcoma from the periosteum forms nodular swellings, while that 
arising within the bone gives a fusiform growth because of its tend- 
ency to spread lengthwise. 

Secondary sarcoma of the bone-marrow is not rare in general 
sarcomatosis. 

Myeloma. — This term has been applied to a form of multiple 
primary tumor of the bone-marrow allied to the lymphatic growths 
of leukemia. The term lymphedema ossea has also been given to it. 
There are three types — the myeloid, in which myelocytes predominate; 
lymphoid, made up chiefly of small deeply staining cells, and the plasma- 
cell type. However, all these cells are represented in each tumor. The 
growths attack the shaft of the bones and fractures or bends may 
occur. 

Chloroma is a form of sarcoma, having a greenish or yellowish 
color, that is met with in the periosteum, especially about the orbits 
and other parts of the skull. 

Primary carcinoma of the bones has been observed in a few 
cases. It can only be explained upon the assumption that islets of 
epithelial tissue have been deposited in the bone by faulty develop- 
ment. Most cases, however, described as primary carcinoma were 
probably in reality alveolar sarcomata. 

Secondary carcinoma of the bones is not rarely met with, espe- 
cially in cases of cancer of the breast, thyroid gland, and prostate. 
The secondary nodules may occupy the periosteum or the bone-marrow. 
The bone becomes exceedingly fragile, and fractures are not infrequent. 

Secondary tumors of bones are commonest as metastases from the 
breast, adrenal prostate, kidney, and thyroid, and involve most fre- 
quently ribs, vertebrae, femur, humerus, and cranium. Thyroid-tumor 
metastases are usually single. 

Cysts and Parasites. — Cystic transformation of myxomata and 
of sarcomata may be met with. Occasionally, dermoid cysts are 
observed. Among the parasitic diseases Cysticercus cellulose has been 
described in a number of instances. 



CHAPTER X 



DISEASES OF THE JOINTS 

Luxation. — The most frequent injury of joints is that known as 
luxation, in which the relations of articulating bones are disturbed. 
In these cases the ligaments and other soft tissues around the joints 
are more or less torn, and in consequence become inflamed. If the 
luxation is reduced, this inflammation subsides quickly, and frequently 
normal conditions are restored. If the luxation persists, various second- 
ary changes may occur. Ankylosis in abnormal positions may take 
place by the formation of fibrous adhesions, or in more favorable cases 
a false joint may be established. In the latter cases local atrophy takes 
place in one of the bones, forming a depression into which the end of the 
other fits. Later, ossifying periostitis produces an elevation around the 
depression of the socket, and thus a well-formed joint may be pro- 
duced. Luxation may be congenital, due to hypoplasia of the joint sur- 
faces or their surrounding tissues. 

Ankylosis is the term applied to the condition in which the normal 
movability between articulating bones is prevented by interosseous 
attachments. Pathologically, ankylosis may be fibrous, cartilaginous, 
or bony. All of these forms are met with after chronic inflammatory 
conditions of the joints. The ankylosis may be due to growing together 
of the joint surfaces by fibrous, cartilaginous, and bony deposits of the 
arthritis, or the fixation may be due to periarticular changes if the same 
pathological processes occur around the joint, as in arthritis deformans. 

DISTORTIONS OF JOINTS 

Distorted conditions of the joints may be due to congenital mal- 
formation, to contractions of the muscles and tendons, or to cicatricial 
tissue in the neighborhood of the articulation. Changes in the joints 
themselves may be present as primary or as secondary conditions. 
Among the more important of such deformities of joints are the various 
sorts of club=foot: pes varus, the sole of the foot turned in; pes valgus, 
the sole of the foot turned out; pes equinus, the foot extended and sup- 
ported upon the anterior ends of the metatarsal bones; pes calcaneus, 
the foot flexed and resting on the heel. Combinations of these condi- 
tions are frequently met with. At the knee-joint are found: genu 
valgum, in which the knees are bent in (knock-knee), and genu varum, 
in which the knees are bent out (bow-legs). 

855 



856 



A TEXT-BOOK OF PATHOLOGY 



CIRCULATORY DISTURBANCES 

Hyperemia of the joints occurs as a part of acute inflammations, 
and involves the synovial membranes particularly. The synovial fluid 
may be increased in quantity. 

Hemorrhage into the joint may result from traumatic causes or 
from inflammatory conditions, particularly in the course of hemor- 
rhagic diseases, notably scurvy and hemophilia. The blood may remain 
fluid for a long time, and the joint not rarely has the appearance of 
chronic arthritis with effusion. Later, resorption of the blood takes 
place. 

Dropsy of the joints occurs in the course of acute and chronic 
inflammations. 

INFLAMMATIONS 

Acute arthritis may be traumatic or due to hematogenous infec- 
tion; in other cases it is secondary to disease in the vicinity. Hema- 
togenous arthritis may occur in the course of various infectious diseases, 
such as scarlet fever, small-pox, pyemia, etc. In the same group must 
be considered acute articular rheumatism, which is doubtless an infec- 
tion conveyed to the joint through the blood. 

Pathological Anatomy. — Various grades may be distinguished, such 
as the dry or fibr inous, the serous, and the purulent. In all cases there is, 
first, a deep congestion, swelling, and infiltration of the synovial mem- 
brane. The ligaments and the cartilage are more or less implicated 
at the same time. The terms synovitis, implying involvement of the 
synovial membrane, and panarthritis, implying general involvement, 
may be applied. In the dry or fibrinous form there is a deposit of fibrin 
upon the surface, with or without serous exudation. In the genuine 
serous form the exudation is purely serous, but more commonly sero- 
purulent liquid is observed. Entirely purulent exudate is sometimes 
formed (empyema of the joints). Acute inflammatory rheumatism is 
a serofibrinous arthritis. 

Results. — In the milder cases complete resolution may take place 
without destruction of the tissues of the joint. In the more serious 
cases there is inflammation of the articulating cartilages, with conse- 
quent ulceration or caries, or even considerable necrosis, of the cartilage. 
The underlying bone may be laid bare, and ostitis or osteomyelitis may 
result. Sometimes discharge of purulent material into the surrounding 
tissues occurs, and fistulous communications with the exterior may be 
established. These processes may lead to extensive disorganization of 
the joints, with luxations and, in later stages, ankylosis. 

Associated Conditions. — About joints the seat of acute inflammation 
there is always a periarthritis or, at least, an edematous swelling. Gen- 
eral systemic infection may follow these acute inflammations of the 
joints. 

Chronic arthritis may be due to a variety of causes. It may follow 
the acute forms already described or may be primarily chronic. Among 



DISEASES OF THE JOINTS 



857 



the more important causes are traumatism and certain infections. It 
occurs in the course of gout and in certain nervous diseases, probably 
as the result of disturbance of the trophic mechanism. Chronic arthritis 
of the aged and arthritis deformans are allied forms of joint disease, prob- 
ably infectious or toxic in many cases. Other factors, such as nervous or 
trophic disturbances, may play a part in the etiology in some cases. 

Pathological Anatomy. — A variety of forms may be distinguished. 
The same etiological factors may, however, give rise to one or another 
in individual cases. 

Chronic serous arthritis, or hydrops articulorum, is frequently due 
to repeated acute arthritis. The joint is filled with thin synovia, and 
the synovial membrane is somewhat thickened. The surface of the 
joint may be more or less covered with 
an injected synovial membrane (synovitis 
pannosa). The knee-joint is most fre- 
quently involved. 

Chronic purulent arthritis is always in- 
fectious, and is usually the outcome of an 
acute seropurulent or purulent arthritis. 
The conditions met with have already 
been described. It terminates in more 
or less extensive disorganization of the 
joint, and in favorable cases in fibrous 
ankylosis (Fig. 412). 

Occasionally, one sees a combination 
of the two preceding forms with tendency 
to scanty exudate, ulceration of the car- 
tilages, and early formation of connective 
tissue. This is the so-called ulcerative 
adhesive chronic arthritis. 

Arthritis Deformans. — This term 
may be used to include a group of con- 
ditions probably of varied etiology char- 
acterized by certain deforming changes 
in the tissues constituting joints, and to an extent also in the adjacent 
bones and ligaments. 

The cartilages entering into the articulation atrophy, and may either 
be uniformly thinned or irregularly indented or furrowed. The articular 
surface may be extremely roughened and irregular. Later, or simul- 
taneously, the edges of the cartilages may present hypertrophic changes. 
Usually, this takes the form of "lipping" or projecting ecchondroses at 
the sides of the joint, sometimes of considerable magnitude. Similar 
hyperplastic cartilaginous change may occur on the articular surface 
or in the synovial tissues, and the ligaments about the joint. 

The bone beneath the articular cartilages or where it has been ex- 
posed by atrophy or erosion of cartilage becomes more or less sclerosed 
(eburnated), or may suffer an atrophic process. Secondary ossification 
of ecchondroses and of the cartilaginous transformations of the soft 




Fig. 412 



Fibrous ankylosis, due 
to chronic purulent arthritis. 



858 



A TEXT-BOOK OF PATHOLOGY 



tissues is sometimes present, and especially in the spine leads to pro- 
nounced disability. 

The synovial membrane and the ligaments about the joints are 
usually affected, and in some cases are the chief seats of alteration. 
Thickening and fibrosis may occasion considerable fibrous ankylosis. 
In some cases villous outgrowths from the synovial membrane are 
abundant, and these may become cartilaginous and may be separated 
as free bodies within the joint. 

Clinical Types. — (a) Arthritis deformans in its most familiar form is 
polyarticular and affects the small joints of the hands and feet primarily. 
Later, though often simultaneously or even before the small joints are 




Fig. 413. — Arthritis deformans, showing extensive deformity of the hands. 

involved, the knees, elbows, and other large joints suffer a similar 
change. This form is most frequently encountered after the third 
decade of life, but may occur in younger persons and even in childhood. 
The disease is insidious in onset and progressive up to the most advanced 
deformity. 

(b) In other cases a more acute onset and more active evidences of 
joint inflammation cause a nearer clinical resemblance to articular 
rheumatism. This form also is usually polyarticular and has practically 
the same distribution as the first type. In the end the joint changes 
may be identical, but not infrequently fibrous tissue growth remains 
predominant in this type. The suggestion of an infection is most 
pronounced in this group. A class of cases, described by Still as occur- 



DISEASES OF THE JOINTS 



859 



ring in young children and associated with glandular and splenic 
enlargement, anemia, and fever, should perhaps be included here. 

(c) Senile arthritis of the hip (malum coxa? senile) and the similar 
types of dry arthritis of the knee and other joints, in which moderate 
cartilaginous erosion and absorption, and atrophic or hyperplastic 
changes in the ends of the bones occur, constitute another group. 

(d) Heberden's nodes are bony enlargements at the sides of the ter- 
minal interphalangeal joints of the fingers. These may occur inde- 
pendently or in association with other joint changes. The process is 
similar to that seen in other types. 

(e) Spondylitis deformans is a deforming and ossifying type of 
arthritis of the spine. In some cases the intervertebral disks become 
atrophic and bony ankylosis takes place between the bodies of adjacent 
vertebrae. In other cases bony 
ankylosis of the smaller articu- 
lations of the spine and ossifi- 
cation of the ligaments is the 
initial process. The spine may 
be rigid and straight, or may 
be markedly kyphotic. Some- 
times the hips and shoulders 
and the articulations of the 
ribs may be involved. 

Nomenclature and Etiol- 
ogy. — The general term arth- 
ritis deformans is preferred as 
sufficiently descriptive, and 
because it involves no theory 
regarding the precise type of 
pathological change or of 
etiology. The old name rheu- 
matoid arthritis is objection- 
able because of the implied 

relationship with rheumatism. Osteo-arthritis, atrophic arthritis, and 
hypertrophic arthritis are terms properly used in some instances, but not 
definitely applicable as separating distinct types. 

The etiology of the forms of joint disease, here included under one 
general term, may be very varied. Formerly, the occurrence of the 
common polyarticular form in persons who had endured hardships, 
exposure, or various kinds of physical and nervous depression, and the 
associated trophic changes in the skin and muscular tissues suggested 
a nutritional disorder or some nervous condition as the important etio- 
logical factor. In recent years attention has been drawn more and more 
insistently to the probability of infection or infectious toxemia. Hidden 
sources of infection (tonsils, teeth, nasal sinuses, gastro-intestinal 
tract) have been discovered in some cases, but not in all. Trau- 
matism undoubtedly plays a part in initiating the disturbance in 
some cases. 




Fig. 414. — Neuropathic arthritis of the knee 
in a case of locomotor ataxia (case of Dr. C. W. 
Burr). 



860 



A TEXT-BOOK OF PATHOLOGY 



Neuropathic arthritis is met with in the course of spinal diseases, 
such as locomotor ataxia and syringomyelia (Fig. 414). It resembles 
the forms just described, is slowly developed, and is usually quite 
painless, suggesting a purely degenerative or trophic disorder. In 
the early stages there is a large amount of exudate, which collects quickly. 
The absorption of the ends of the bone is more marked than in arthritis 
deformans. 

Gouty Arthritis. — Gout is a constitutional disease with a tend- 
ency to a peculiar form of arthritis. The latter consists in the deposit 
of crystals of urate of sodium and calcium in the cartilage cells and 
intercellular substance of the articulations, and in more advanced 
cases in the connective tissue of the joints and the tissues round the 
joints (Fig. 415). These crystalline deposits occur in definite attacks, 

as a rule, each attack {gouty paroxysm) 
§||l||jjjl being marked by inflammatory proc- 
j| . esses in the joint. Hyperemia of the 

. | synovial membrane, with serous effu- 
I if; sions and with sometimes more evi- 
;| dent inflammatory manifestations 
(hyperplasia of the cartilage cells and 
round-cell infiltration), is observed 
during the paroxysms, and by their 
Fig. 415.— Deposit of crystals of repetition chronic changes in the joint 

urate of sodium in an articular cartil- i i m, . ., 

age (Lancereaux). are produced. I he cartilages may 

become more or less eroded, and even 
carious changes and suppuration may take place. The joints most fre- 
quently involved are the small joints of the hands and feet, notably 
the metatarsophalangeal joint of the great toe. The larger articulations 
are less commonly involved, and usually after the smaller joints. 

Associated Conditions. — The pathology of gout is by no means 
confined to the changes in the joints. The disease is a general one, and 
pathological changes are found in various organs. There is a tendency 
to thickening of the blood-vessels, to atheroma, and to sclerotic changes 
in the kidney, liver, and heart; and uratic deposits may occur in the 
organs named or in the subcutaneous tissue or superficial cartilages, 
such as those of the ear and nose {gouty tophi). Concretions or calculi 
are frequently formed in the kidney or bladder. 



INFECTIOUS DISEASES 



Tuberculosis 



Tuberculosis, when primary in the joints, usually begins in the 
synovial membrane. Occasionally, it arises by extension from lesions 
in the soft parts of the immediate vicinity or, more commonly, it is 
secondary to tuberculosis of the adjacent bone, from which source any 
part of the joint may be first involved. 



PLATE 15 




Gouty tophi in ear. 



DISEASES OP THE JOINTS 



861 



Etiology. — Tuberculous arthritis is most frequent in childhood, 
and occurs in those predisposed by heredity. The immediate deter- 
mining cause may be traumatism, this serving to localize the disease in 
a joint rendered peculiarly susceptible. Lesions in the spongy bone, 
the result of vascular disease, seem to precede joint tuberculosis in 
many cases; the course as outlined under bone tuberculosis is undoubt- 
edly the most frequent path of infection. 1 Tuberculous arthritis is 
frequently secondary to scrofulous disease of the skin or glands, or to 
pulmonary tuberculosis, but is often primary in the joint or adjacent 
bone ends. 

Pathological Anatomy. — The changes met with in the joints 
vary somewhat in different cases. In instances beginning in the syno- 
vial membrane there are formed more or less abundant, soft, spongy 
granulations, which may eventually fill the entire joint cavity. These 
are pinkish or whitish in color, and may show gray or yellow spots or 
tubercles quite plainly. Later, this granulation tissue tends to degen- 
erate, becoming mucoid or breaking down by suppurative or cheesy 
change. In the early stages the soft tissues of the joint are considerably 
inflamed and edematous; later, they may show ulcerative or necrotic 
change, and similar alteration may occur in the articular cartilages. 
Puriform softening of the granulations and the tissues of the joint may 
lead to the development of cold abscesses within the joint, and the 
latter may eventually burrow to the exterior. In cases progressing 
unfavorably the joint is greatly disorganized by the advancing necrotic 
changes. The abnormal productions are either discharged or inspis- 
sated, and ankylosis of the joint by fibrous adhesions takes place. 

The external appearances of tuberculous joints are often quite dis- 
tinctive. The joint is swollen and boggy ("white swelling") or some- 
what elastic to the touch, and usually more or less distorted from sub- 
luxation. There is little evidence of acute inflammation. In cases 
terminating in ankylosis the bones are generally left in faulty position 
in consequence of the formation of adhesions and the irregular contrac- 
tions of muscles. 

Secondary Disorders. — Long-standing tuberculosis of the joints 
occasions profound disturbances of the general health and sometimes 
causes definite disease, such as amyloid degeneration of various organs. 
Disseminated tuberculosis rarely results. 

Syphilis 

Syphilitic disease of the joints may occur in hereditary lues. The 
cartilages of the joints are eroded, and thickening of the ligaments 
with puriform exudation into the joint is observed. The phalangeal 
articulations are most frequently involved. In later life gummata in the 
neighborhood of the joints may invade the latter by contiguity. 

1 The cases arising by primary involvement of the synovial fringes are often 
rather acutely inflammatory in character with a serous exudate, while those cases 
which extend from the ends of the bones are more protracted in their course, and are 
usually accompanied by rarefying or sclerosing osteitis about the tuberculous lesion. 



862 



A TEXT-BOOK OF PATHOLOGY 



TUMORS 

Hyperplastic conditions are met with in the synovial fringes of the 
joints in association with arthritis or independent of such. These 
hyperplasias may take the form of fibrous growths, or they may become 
lipomatous. An interesting form of new growth is seen in the so-called 
rice-bodies or "joint-mice." These are small fibrous or cartilaginous 
bodies, up to the size of a small nut, which are entirely free in the joint 
or attached by a fine pedicle to the synovial membrane. They are 
formed from the synovial fringes, and probably result from injury or 
hypertrophic inflammation in most cases. They may be remains of 
blood-clots or broken-off polypoid hyperplastic synovial membranes. 
Occasionally, they undergo calcareous change. The joints may be 
secondarily involved in various forms of bony tumors. 

THE TENDON-SHEATHS AND BURS.E 

Inflammations of the sheaths of tendons (tenosynovitis) and of the 
bursae (bursitis) occur under similar circumstances and in similar forms 
as inflammations of the joints. A form of chronic bursitis with dropsical 
effusion frequently occurs in the bursa beneath the patella from chronic 
irritation (housemaid's knee), and in the bursa at the joint of the elbow 
(miner's elbow) . These conditions are analogous to hydrops articulorum. 
Gout gives urate deposits in the tendons, their sheaths and bursse, with 
considerable exudate or infiltration or even-necrosis. 

Ganglion is a condition of the tendon-sheaths of some clinical 
interest. It presents itself as a rounded cystic nodule, most frequently 
upon the back of the hands and wrists. Distinct fluctuation may be 
discovered, or the cyst may be so dense that it feels stony hard. The 
ganglion results from a localized dropsical condition of the sheath of the 
tendons, with frequently a lateral hernious projection. A similar con- 
dition is sometimes caused by projection of the synovial membrane of 
the joints. This condition is sometimes tuberculous, occasionally 
primary in a clinical sense, at other times secondary to bone tubercu- 
losis. This form contains rice-bodies. 

Tumors are rare, but a so-called myeloma, which seems more like 
an endothelioma, has been reported. 



CHAPTER XI 



DISEASES OF THE VOLUNTARY MUSCLES 

Congenital malformations are occasionally met with, such as 
absence of a part or of an entire muscle. 

HYPERTROPHY 

Hypertrophy is frequently produced by athletic exercise or labor- 
ious occupations. This affects the parts brought into play, and is pro- 
portioned to the amount of work and the constitution or condition of 
the individual. The muscle-fibers increase in thickness and probably 
also in number. 

Sometimes muscular hypertrophy is met with in cases in which no 
adequate cause is discoverable. Thus in local or general giant growths 
the muscles may be involved with other parts. 

Pseudohypertrophy will be discussed among the degenerative condi- 
tions. 

CIRCULATORY DISTURBANCES 

Anemia of the muscles may be part of a local or general anemia; 
it is often quite insignificant in comparison with anemia of other parts. 
In some of the general anemias the muscles may present a dark appear- 
ance, due to degenerative conditions. 

Hyperemia is physiological during and after exercise. It occurs as 
an active process in association with inflammatory conditions and as a 
passive congestion in cases of vascular stasis. 

Hemorrhages may be traumatic, or may result from rupture of the 
vessels in consequence of inordinate blood-pressure or local degenera- 
tion of the vessel walls and the surrounding muscle-fibers. Among the 
conditions in which hemorrhage takes place are tetanus and other con- 
vulsive disorders, fevers, and hemorrhagic diseases such as scurvy or 
hemophilia, and septic diseases. The hemorrhages may occur in the 
form of small extravasations between the fibers, or of more extensive 
infiltrations in the intermuscular planes. In cases of traumatism, 
scurvy, or hemophilia, considerable blood-tumors may be formed, the 
muscle-fibers being pushed aside or torn apart. The blood is more or 
less rapidly absorbed. Pigmentation and fibrous-tissue proliferation 
may result. 

Embolism of the arteries or thrombosis of the veins does not pro- 
duce serious disturbances, as a rule. In cases of embolism, secondary 
results may follow if the embolism is infective. 

863 



864 



A TEXT-BOOK OF PATHOLOGY 



INFLAMMATIONS 

Inflammation of the muscles, or myositis, may be acute or 
chronic, and may present itself in a variety of forms. Acute myositis 
may be local or disseminated. 

Localized Acute Myositis. — This form may be due to injuries, 
such as contusions of the muscles or wounds communicating with them, 
or may be infectious in character, resulting from the direct extension 
of infectious diseases of the skin, subcutaneous tissues, bones, and other 
adjacent parts, or from embolism. A serous, a hemorrhagic, and a 
purulent form may be distinguished. 

Serous myositis is characterized by an edematous condition of the 
muscle, which gives it a peculiar gelatinous appearance on section. 
Microscopically there is cellular infiltration of the muscle-bundles, 
while the muscle-fibers themselves become swollen and suffer granular 
degeneration or hyaline change, and sometimes vacuolation. 

Hemorrhagic myositis is an intense form, and is met with in muscles 
adjacent to gangrenous or phlegmonous lesions, malignant pustules, and 
the like. Myositis occurring in scorbutic individuals is frequently of 
the hemorrhagic form, as is also that which occurs in consequence of 
the sting of venomous snakes or other animals. The muscle becomes 
more or less tensely swollen, and on section the hemorrhagic infiltra- 
tion is plainly visible as a diffuse process or as localized areas of hemor- 
rhage. 

Suppurative myositis may be circumscribed or diffuse. Circum- 
scribed myositis, or abscess of the muscle, may result from entrance 
of micro-organisms through the lymphatic or vascular circulation, or 
it may be due to traumatism, with communications from the surface. 
Occasionally suppurative inflammation occurs in an obscure manner, 
when the term cryptogenetic myositis is applicable. Distinctly metas- 
tatic abscesses may be occasioned by embolism. 

In association with suppurative inflammations of the skin or sub- 
cutaneous tissues and the mucous membranes there may be seropur- 
ulent or phlegmonous myositis, with the formation of irregular abscesses. 
In these cases the lesion spreads by infiltration, and the muscle-fibers 
undergo widespread degeneration (fatty degeneration, hyaline change, 
and necrosis). Abscesses in the muscles extend and rupture in various 
directions, and may leave considerable areas of scar-formation. 

Disseminated acute myositis or polymyositis may appear without 
any definite cause, sometimes in association with tuberculosis of the 
lungs, or as a distinctly secondary affection in association with infec- 
tious diseases, like typhoid fever, diphtheria, etc. In the primary form 
there may be widespread muscular disease, with swelling and tenderness 
of the muscles and sometimes redness and edema of the skin. The term 
pseudotrichinosis was applied from the resemblance of the appearances 
to those of trichinosis, and the name dermatomyositis has also been 
given this condition. In several cases this disease has been shown to be 
a bacteremia due to a form of Staphylococcus pyogenes, the organism 



DISEASES OF THE VOLUNTARY MUSCLES 



865 



having a predilection for the muscles, as indicated by animal ex- 
perimentation. Some of the conditions included under the heading 
muscular rheumatism by clinicians are doubtless instances of the kind 
here discussed. Examination of the muscles shows pallor of the tissue 
and sometimes visible areas of degeneration. Microscopically there 
are cellular infiltration between the muscle-fibers and swelling, with 
loss of striation of the fibers themselves. More advanced degenerations 
of the fibers, such as granular change, coagulation-necrosis, and vacuola- 
tion, may be observed. The affected muscles lose their functional con- 
tractile power, and more or less palsy results. When affecting the 
muscles of the pharynx and respiration this becomes serious in predis- 
posing to inspiration pneumonias. 

The condition described as secondary acute polymyositis is degen- 
erative to a greater extent than inflammatory, and will be considered 
among the degenerations. 

Chronic myositis may be suppurative in type or productive. 

Chronic suppurative myositis may be the outcome of acute sup- 
puration, and is particularly frequent in association with tuberculosis 
and actinomycosis. 

Chronic productive myositis is characterized by the formation of 
connective tissue between the muscle-fibers. The fibers themselves, 
as a rule, undergo degenerative changes, though occasionally showing 
regeneration to some extent. This condition may be the termination 
of acute myositis, or it may occur in the vicinity of various localized 
diseases of the muscles or of the neighboring parts. In some cases, if 
not all, the primary change is degeneration of the muscle-fibers, and the 
interstitial or fibrous tissue is reactive in character. Some of the cases 
will be considered under the head of muscular atrophies. The changes 
that occur in the interstitial tissue of the muscles consist primarily of 
proliferation and round-celled infiltration. Later, there is formation 
of firm connective tissue. Some multiplication of the muscle-nuclei 
and actual increase in size of some muscle-fibers may be observed. 
Degeneration of the muscle-fibers, however, is more prominent, and is 
generally in proportion to the degree of connective-tissue change. 
The fibers may show cloudy swelling or hyaline changes, or more com- 
plete degeneration, such as fatty degeneration, fragmentation, or vacuole 
formation. 

Ossifying myositis is a variety of productive myositis. It may 
occur in the form of bony nodules in parts subjected to constant irri- 
tation or strain, as in the case of the deltoid muscle in soldiers and the 
adductor muscles in horsemen. Similarly, in the vicinity of disease of 
the bones and periosteum, nodules may develop in the muscle. A form 
of more general disease, termed myositis ossificans progressiva, has been 
observed in youthful persons, without discoverable cause. It affects 
the muscles of the back and neck, and sometimes those of all parts of 
the body. The muscles are swollen, and first present inflammatory 
manifestations, terminating in fibrous change which finally leads to 
bone-formation. The osseous tissue is at first in the form of spicules or 

55 



866 



A TEXT-BOOK OF PATHOLOGY 



small nodules, but gradually increases to considerable proportions. The 
muscles themselves contract, and various deformities with pseudo- 
ankyloses may result. The muscles of the face, diaphragm, and 
heart are unaffected. A peculiar malformation has been found asso- 
ciated with 75 per cent, of the cases. This is a form of microdactylism — 
ankylosis of the phalanges of the thumb and lack of one phalanx of the 
great toe on both sides. 

ATROPHY AND DEGENERATIONS 

Several forms of atrophy are recognized. Certain cases are depend- 
ent upon disease of the spinal cord or nerves (neuropathic form), others 
occur as primary diseases of muscles (myopathic form), and in another 
group the change is due to simple nutritional processes (simple and 
senile forms). 

Neuropathic muscular atrophy may be the result of disease of 
the anterior horns of the gray matter of the cord or of neuritis. To the 
cases in which this lesion is the underlying pathological condition the 




Fig. 416. — Neuropathic muscular atrophy, showing atrophy of the muscle-fibers, increase 
in the interfascicular fibrous tissue, and thickening of the blood-vessel walls. 

term progressive muscular atrophy has been applied. The causes of this 
disease are obscure. 

It leads to progressive atrophy of the muscles of the hands, arms, 
and shoulders, and less frequently of those of the body and buttocks. 
It usually begins in the small muscles of the hands, but sometimes 
affects those of the shoulders first. The muscles become pale and rather 
flabby. Microscopically, the fibers show various forms of degeneration. 
Fragmentation in a longitudinal or in a transverse direction, coagula- 
tion-necrosis, and occasionally fatty degeneration of the fibers may be 
seen. Sometimes the fibers seem to grow smaller by a simple atrophic 
process (Fig. 416). Coincidently, reactive proliferation is seen in the 
connective tissue between fibers, and doubtless this to some extent 



DISEASES OF THE VOLUNTARY MUSCLES 



867 



causes further muscular degeneration. The muscle-cells themselves 
may proliferate quite extensively. 

Secondary neuropathic muscular atrophies may occur in various 
spinal diseases, such as syringomyelia and in degenerations following 
cerebral disease. These are essentially similar in character to the 
primary neuropathic variety, though their clinical character is different. 
Section, disease, or injury of motor nerves may lead to local atrophies 
by separating the muscles from their trophic centers in the cord. 

Myopathic muscular atrophy occurs in children and young 
persons, and is frequently hereditary. It begins in the buttocks, thighs, 
or calves, and sometimes in the shoulders. Two forms have been dis- 
tinguished: the simple atrophic form and the pseudohypertrophic form. 
The anatomical changes in the former are the same as in the neuropathic 
variety just described. 

Pseudohypertrophic Muscular Atrophy. — In this condition the 
muscles increase greatly in size, but are soft and flabby. The child 
may present the appearance of an athlete, with enormous calves and 
thighs, but is extremely weak and can scarcely stand. Microscopically, 
the causation of the enlargement is found to be a considerable degree of 
intermuscular proliferation of connective tissue, with marked fatty infil- 
tration. Sometimes in this form, as well as in other varieties, some 
actual enlargement of the muscle-fibers is observed, but this is doubtless 
degenerative. 

To this group probably belongs the myotonia congenita of Thomsen. 
In this form some fibers are definitely hypertrophic, but the general 
muscular mass is atrophic. A suggestion of hyperplasia is given by 
increase of nuclei, but this may arise from fiber splitting. 

Simple muscular atrophy may be senile in origin or due to lack 
of exercise. In these cases the muscle-fibers become smaller, and some 
proliferation of the connective tissue is generally present. In senile 
cases brown atrophy may occur, brownish pigment particles being 
deposited in the atrophic fibers, especially near the nuclei. 

Parenchymatous degeneration of the muscles may occur in the 
vicinity of inflammatory lesions, tumors, or other areas of disease. 
It may also occur in the course of infectious diseases in association with 
coagulation-necrosis. The fibers become cloudy and lose their striated 
appearance from the presence of minute granules. In some instances 
inflammatory changes in the interfascicular connective tissues are asso- 
ciated with the degeneration of the fibers. Cases of this sort may be 
called secondary acute polymyositis. 

Fatty degeneration is found under the same circumstances as the 
above, and also in chronic cachectic diseases and in cases of poisoning 
with phosphorus and other "parenchyma poisons." The muscle- 
fibers have a streaked or spotted, yellowish appearance, and are more 
or less flabby. Microscopically, the fibers are seen to be filled with 
small oil-droplets which obscure the striations. All parts of the fiber 
may become degenerated until the sarcolemma sheath contains only a 
mass of fat-droplets and detritus (Fig. 418). 



868 



A TEXT-BOOK OF PATHOLOGY 



Fatty infiltration may occur in association with atrophy in the 
condition above described — pseudohypertrophic muscular atrophy ; and 
in various nervous diseases in which the muscles waste from disease 
■ . or trophic change. A certain 

amount of lipomatosis may oc- 
cur in general obesity. This 
2l fat increase also occurs in cases 




of abnormal carbohydrate me- 
tabolism. 

Amyloid degeneration is 

rare and unimportant. 

Calcification may occur in 
the form of ossifying myositis, 
and locally in scars following 
various local diseases — ab- 
scesses, etc. 

Coagulation=necrosis, or 
hyaline degeneration, is of 
great clinical importance. It 
was first discovered by Zenker 
as one of the lesions occurring 
in typhoid fever. The muscle- 
fibers at first become granular 
and cloudy {parenchymatous 
degeneration), and later waxy or hyaline change occurs in streaks or 
completely transform the fibers. Transverse fragmentation is common, 



- ■ '...at- 



Fig. 417. — Muscle from a case of carcinoma 
of the esophagus, showing the presence of fat and 
pigment at the ends of the nuclei. From a draw- 
ing. X 1000. (Jewesbury and Topley, in Jour- 
nal of Pathology and Bacteriology.) 





Fig. 418. — Section from a case of infective purpura, showing well-marked true fatty 
degeneration. From a drawing. X 450. (Jewesbury and Topley, in Journal of Path- 
ology and Bacteriology.) 



and gross rupture of the muscle may be found. In the latter cases 
hemorrhagic infiltration, or even considerable hemorrhage (hematoma), 



DISEASES OF THE VOLUNTARY MUSCLES 



869 



may be occasioned. Reactive inflammatory change in the interstitial 
connective tissue is generally present. This disease occurs in the course 
of typhoid fever, but also in various other febrile and infectious condi- 
tions. It is most common in the abdominal muscles (rectus abdomi- 
nis), in certain muscles of the extremities, and in the heart. The latter 
situation is, of course, of greatest significance. (See Diseases of the 
Heart.) 

INFECTIOUS DISEASES 

Tuberculosis may occur in the form of cold abscesses in associa- 
tion with tuberculous disease of bone or less frequently of the lymphatic 
glands or other parts. In these cases there is a gradual extension of the 
caseous and liquefying tuberculous disease into the muscles, and some- 
times the abscesses burrow to great distances within the muscular sheath, 
as, for example, in psoas abscess. Less destructive tuberculous myositis 
may occur in the muscles beneath the skin and mucous membranes by 
extension of tuberculous processes. In these cases cellular infiltration 
and tubercle formation, with some caseous change, may be observed. 
Miliary tubercles, or larger tuberculous nodules due to hematogenous 
infection, are rare. 

Syphilis may occur in the form of gummata, and it is likely that 
some cases of diffuse productive myositis are syphilitic in nature. 
As in other parts of the body, the blood-vessels in these cases have 
been described as particularly thickened. 

Glanders, actinomycosis, and anthrax may involve the muscles 
in the vicinity of the specific lesions. Nodular and, later, necrotic or 
suppurative foci are the lesions observed. 

TUMORS AND PARASITES 

The tumors of muscles, for the most part, spring from the inter- 
stitial connective tissue. Among the benign tumors fibromata, myxo- 
mata, and lipomata are sometimes met with. Osteoma and chondroma 
are found as localized lesions resulting from irritation or as true tumors. 
Striped muscle tumors, or rhabdomyomata, are rarely found in the 
muscles, though occasionally seen as small nodules. 

More important than the above is sarcoma, which occurs as a pri- 
mary tumor comparatively frequently. The fibrous and spindle- 
celled varieties are common, and round-celled sarcoma are sometimes 
observed. The tumors originate from the connective tissue, though 
it is held by some that the muscle-fibers themselves may undergo 
sarcomatous transformation. 

Carcinoma is a rare tumor, and is always secondary. The second- 
ary form is not rarely seen in the muscles in the vicinity of carcino- 
mata of other structures, such as the mammary gland. 

Among the parasitic diseases of muscles may be mentioned trich- 
inosis, cysticercus invasion, and hydatid disease. The first occasions 
disseminated myositis, to which reference has already been made. 
The other two conditions are rare and not important. 



CHAPTER XII 



DISEASES OF THE BRAIN AND ITS MEMBRANES 
The Dura Mater 

The dura mater forms the inner covering of the skull and acts as a 
firm support of the brain. It consists of dense connective tissue; 
and is poor in blood-vessels, but reflections of the membrane surround 
large venous sinuses. 

CIRCULATORY DISTURBANCES 

Active hyperemia occurs in the dura in association with tumors, 
gummata, and other focal diseases. The vessels of the dura, surround- 
ing the area of disease become distended and the membrane may be 
diffusely reddened. 

Passive hyperemia may occur under the same circumstances as 
the above, and also in cases of thrombosis of the venous sinuses. 

Hemorrhages are usually due to traumatism, and may occur on 
the outer or inner surface of the dura. Extradural hemorrhages are 
more common than intradural, especially in cases in which there is 
fracture of the skull. The blood in these cases comes from the skull 
bones and the vessels on the outside of the dura. It does not collect 
quickly, and tends to gravitate to dependent parts. It exerts pressure 
by its bulk, and may cause cerebral degeneration beneath it. A collec- 
tion of blood between the skull and the dura is sometimes designated 
internal cephalhematoma. Small hemorrhages into the dura may occur 
in infectious or hemorrhagic diseases and in cases of death from asphyxia. 

Sinus Thrombosis. — This condition, like other thromboses, is due 
to altered blood or vessel states, or to inflammation, of which the last 
is most important. Traumatism and infections are the commonest 
causes; the former usually produces the formation of a clot in the longi- 
tudinal sinus, while the lateral sinus is most often involved by extension 
of infections from the mastoid cells. Infective thrombi are prone to 
lead to septicopyemia. Surrounding parts are at first edematous, then 
inflamed. The clot is usually soft and necrotic, but may be laminated. 
Thrombi in the dural sinuses have a peculiar tendency to spread rap- 
idly by extension. 

INFLAMMATIONS 

Inflammation of the dura, or pachymeningitis, may be acute or 
chronic, and hemorrhagic, suppurative, or productive in character. 

Internal hemorrhagic pachymeningitis occurs more frequently in the 
aged than in the young, and is not uncommon in the insane. Chronic 

870 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



871 



alcoholism and traumatism seem to be etiological factors of some im- 
portance. In the early stages of the disease the inner surface of the 
dura exhibits a superficial deposit or membrane of grayish color, with 
brown or red spots, the former being composed of altered blood-pigment 
(hematoidin). Often several layers are present, indicating successive 
exacerbations. Microscopically, the membranous deposit is found 
to consist of soft granulation tissue containing numerous thin-walled 
blood-vessels. Later, diapedesis of blood-corpuscles, or actual hemor- 
rhages, occur, and the diseased area may have the appearances of a 
simple collection of blood or of a more or less stratified hemorrhagic 
exudate. Sometimes the amount of exudate and of hemorrhage may 




Fig. 419. — Nodular tuberculous pachymeningitis. The mass to the left is the prod- 
uct of the chronic change in the dura and fitted into the depression in the hemisphere 
(from a specimen in the collection of Dr. Allen J. Smith). 

be such as to cause considerable cerebral compression, and in other cases 
death may occur from the hemorrhage itself. Occasionally the blood 
is in part absorbed, and a serous collection (hydroma duroe matris) 
results. The seat of the disease is usually in the area of distribution 
of the middle meningeal artery. The process is slow, and recurs or is 
continued by irritation of the granulation tissue. The dura grows 
internally by diffuse or localized thickening, but rarely adheres to the 
pia arachnoid. 

Suppurative external pachymeningitis may occur in consequence 
of injuries, caries, or other diseases of the skull. Sometimes it results 
from purulent softening of thrombi in the venous sinuses, and very 



872 



A TEXT-BOOK OF PATHOLOGY 



rarely it is secondary to leptomeningitis. Not rarely localized suppu- 
rative pachymeningitis results from disease of the middle or internal 
ear, with extension through the petrous bone. The dura becomes 
thickened by cellular infiltration, is soft and edematous, and not rarely 
undergoes necrotic change. The disease may be localized or diffuse, 
and may occasion secondary thickening and adhesions of the dura in 
cases terminating favorably. 

Productive pachymeningitis may be of fibrous or ossifying charac- 
ter. The etiology is often obscure. Some cases follow hemorrhagic or 
suppurative pachymeningitis; in others the process seems to be primarily 
productive. Traumatism may cause proliferation of fibrous tissue in 
the dura. This is especially apt to occur after fractures of the skull in 
children, when, as a result of its adhesion to the bone, the dura is almost 
invariably torn. Syphilis is probably a cause of importance. The dura, 
in the fibrous variety, is simply thickened and more or less attached to 
the pia-arachnoid and the inner surface of the skull. When firm attach- 
ments with the skull are formed, osteophytes are frequently found 
upon the surface of the bones and in the dura (ossifying pachymenin- 
gitis). Osseous plates may be met with in the falx cerebri and ten- 
torium cerebelli. 

INFECTIOUS DISEASES 

Tuberculosis may occur in the form of miliary tubercles in asso- 
ciation with tuberculous leptomeningitis. It may also be associated 
with tuberculosis of the bones; and, in rare instances, has been met with 
as a primary disease of the dura. In the latter cases the disease takes 
the form of a caseous nodular thickening of the membrane (Fig. 419). 

Syphilis may occasion a form of diffuse productive pachymeningitis, 
or gummata. The latter may originate in the dura and extend to the 
pia or skull bones, or they may originate in the bones and invade the 
dura secondarily. Gummata in this situation present themselves as 
more or less flattened nodular growths of grayish color, having a marked 
tendency to caseous change and to resolution, with formation of cir- 
cumscribed thickenings and adhesions of the dura. 

TUMORS 

Tumors of the dura mater occur with considerable frequency. 
Among the pathologically benign growths are fibroma, osteoma, and 
chondroma. The most common tumor is probably some form of sar- 
coma. The alveolar variety may occur in various situations, either as a 
flat swelling or as a somewhat pyramidal mass, with the apex toward 
the brain, into the substance of which it projects; it is often firmly 
attached to the skull. Other forms of sarcoma are angiosarcoma 
and the small round-cell variety, which is usually multiple and the result 
of metastasis from some other part. The latter tumors are usually 
flat, diffuse, and often extensive. They may or may not cause bulging 
of the skull. 



DISEASES OF THE BRAIN AND ITS MEMBRANES 873 

Statistical studies have shown that endotheliomata are among the 
most common tumors in this region. They usually occur as single 
irregular masses; but occasionally they are multiple, and it is possible 
that in these cases metastasis has occurred. Ordinarily they produce 
no disturbances in the brain, but in some instances pressure-symptoms 
have been reported. In any of these forms, but particularly in those in 
which the fibrous connective tissue is in excess, calcareous infiltration 
is not uncommon (psammoma) . In nearly all cases these tumors pro- 
duce erosion of the inner surface of the skull. Hyaline degeneration of 
the intercellular substance is very common. 

Among the other tumor-like growths are fibrous changes that may 
or may not be inflammatory in nature, and lead to circumscribed or 
diffuse thickening of the dura mater, and usually cause it to adhere 
densely to the skull. These are most apt to be found in old people. 
In addition to the round-cell sarcoma, gliosarcoma of the brain and 
carcinoma of the scalp may give rise to secondary growths in the dura 
mater, but these are extremely rare. 

CYSTS 

Cysts of the dura are usually due to its protrusion through the 
skull and the escape of cerebrospinal fluid into the protruded por- 
tions. This is spoken of as meningocele. Two varieties are recognized, 
true and false. True meningocele is produced by the bulging of the 
dura mater through some congenital fissure in the skull. It is difficult 
to distinguish this from encephalocele (q. v.). False or spurious meningo- 
cele is almost invariably the result of some injury before the third year 
of life, such as fracture of the skull and effusion of blood. Later the 
blood is absorbed and replaced by a clear fluid, leaving only a brown- 
ish layer upon the inner surface of the cyst. As in early life the dura 
is adherent to the skull, it is usually torn at the time of fracture; and 
ordinarily there is also a laceration of the arachnoid, allowing the 
escape of the cerebrospinal fluid into the sac, which is formed externally 
chiefly by the pericranium. As a result of pressure, of bone absorption, 
or of defective growth, the opening in the skull usually enlarges con- 
siderably, and ultimately there is extreme deformity of the head. In 
cases where the brain has been lacerated at the time of injury, poren- 
cephalic cavities may occur, which in some instances have communi- 
cated with the lateral ventricles. The commonest situation for these 
cysts is the parietal bone ; but they may occur in the frontal or occipital 
regions, and in rare cases are multiple. 

THE PlA-ARACHNOED 

This composite tissue consists of two layers anatomically, but be- 
cause of their close physical and physiological relations are to be con- 
sidered as one membrane. The outer layer, the arachnoid, consists of 
loose connective tissue full of spaces continuous with the perivascular 



874 



A TEXT-BOOK OF PATHOLOGY 



channels of the pia; in these spaces is a limpid fluid, the cerebrospinal 
fluid. The pia follows the convolutions of the brain very closely, and 
there is intercommunication of the vessels of this covering and of the 
choroid plexus. From these facts it is easy to see how infections of the 
pia-arachnoid may extend inward. 

CIRCULATORY DISTURBANCES 

Anemia of the pia may occur in cases of general anemia. 

Active hyperemia is constantly present in the early stages of men- 
ingitis. It is also met with in cases of death from alcoholism and in 
severe infectious fevers, though in most of these cases microscopical 
examination discloses the fact that the process is really one of begin- 
ning inflammation. The pia is red and the small arterioles are injected. 
The fluid in the subarachnoid space is in excess, and may be slightly 
turbid or sanguinolent. 

Passive hyperemia occurs in cases of general venous stasis, as in 
heart disease, pulmonary disease, and venous thrombosis. The large 
veins are greatly swollen, and the subarachnoid fluid is excessive. 

Hemorrhages. — Small punctate hemorrhages may occur in cases 
of meningitis, in scurvy, purpura, and the like. Larger hemorrhages 
between the pia and arachnoid are most commonly due to trauma- 
tism, and may sometimes be the result of rupture of aneurysms. Punc- 
tate hemorrhages are said to occur during severe infections and upon 
absorption to leave small opaque areas in the pia; such white spots are 
indeed frequently seen at autopsy. The blood in cases of large hemor- 
rhages may cause injurious cerebral compression, if death does not 
follow the injury itself. Occasionally the blood becomes inspissated 
and absorbed, the membranes in these instances becoming thickened 
and pigmented, or it may be encapsulated and the pigment absorbed, 
giving rise to a clear cyst (hygroma). 

Edema of the membranes, or collections of liquid in the subarach- 
noid space (external hydrocephalus) may be due to passive congestion. 
The membranes are thickened and of a translucent or gelatinous appear- 
ance ; the subarachnoid fluid causes elevation of the arachnoid and more 
or less compression of the cerebral convolutions. Hydrops ex vacuo is a 
form of dropsical effusion under the arachnoid, resulting from atrophy 
or hypoplasia of the cerebral convolutions. The space normally occu- 
pied by cerebral substance is in these cases filled with cerebrospinal 
liquid. 

INFLAMMATION 

Inflammation of the arachnoid and pia is called leptomenin= 
gitis. It is always an infectious process, and may be either acute or 
chronic. 

Etiology. — The commonest cause of sporadic acute leptomeningitis 
is the pneumococcus. It is found in about 60 per cent, of all cases, and 
in these pneumonia is often an associated or primary condition. The 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



875 



pneumococcus may reach the meninges either by the blood- or lymph- 
channels, or by creeping along the lymphatic spaces in the areolar tissue 
between the esophagus and vertebral column; occasionally it enters 
directly from the ear or nasal cavity. Other micro-organisms that 
have been found are the streptococcus, the staphylococcus, Fried- 
lander's bacillus, the Bacillus pyocyaneus, the bacillus of glanders, the 
influenza bacillus, the actinomyces, the typhoid bacillus (of which a 
number of cases have been reported), the Bacillus coli communis, and 
the bacillus of bubonic plague. Meningitis occasionally occurs in the 
course of gonorrhea in which the gonococcus is probably the bacterial 
cause, although this has been questioned. Mixed infection is not un- 
common, consisting usually of the pneumococcus and one or other of 
the more common pyogenic micro-organisms, and the latter are also 




Fig. 420. — Leptomeningitis purulenta cerebralis (Karg and Schmorl). 



frequently found associated with the tubercle bacillus. The cause of 
epidemic cerebrospinal meningitis is the Diplococcus intracellularis 
meningitidis, discovered in 1887 by Weichselbaum in six cases that he 
examined, and subsequently found in other cases by Goldschmidt, 
Guarnieri, Netter, Faber, and others. 

Pathological Anatomy. — The gross changes may vary from those 
that are not recognizable macroscopically to collections of greenish 
pus in the subarachnoidal space one-half inch or more in thickness 
and covering the entire surface of the brain. In the slightest forms the 
presence of the condition may be suspected by the slight edema of the 
arachnoid, and perhaps a small collection of fluid containing flakes 
along the fissures of the brain. In some cases, however, even this does 
not occur, and it is impossible, without a microscopical examination, to 



876 



A TEXT-BOOK OF PATHOLOGY 



say that inflammatory processes exist. Microscopically, sections in 
these cases usually show overfilling of the small vessels with blood, and 
a greater or less number of round cells, usually polynuclear, imme- 
diately surrounding it. Often this collection of round cells is most 
marked in the recesses of the convolutions. Staining for bacteria usually 
reveals the presence of a few, although in these cases they are rarely 
numerous. If the process has been more severe, or of longer duration, 
the edema of the arachnoid becomes more pronounced, its glassy, moist 
appearance being very distinctive. The vessels are usually injected; 
this applies particularly to the veins, which appear as dark-blue tor- 
tuous cords running through the membranes. In the arachnoidal space 
there is now a considerable collection of fluid, and along the sides of the 
arteries usually a distinct collection of lymph or pus. Sometimes, but 
not always, the arterioles are also distinctly injected, and occasionally 
there is a faint pinkish coloration, due to the injection of the capillaries. 

This form may be localized or diffuse, and is almost always secondary 
to some local source of inflammation, which is most frequently middle- 
ear disease. The process often shows distinct indications of rapid 
extension, and may spread to the lining of the ventricles and cause an 
internal collection of fluid. 

The diffuse forms have been divided, according to the part affected 
with greatest intensity, into leptomeningitis of the vertex and lepto- 
meningitis of the base. The processes are by no means limited to these 
areas, however, but may extend in any direction. It is common for the 
suppurative lesions to spread along the arachnoid spaces to the spinal 
meninges. The ventricles may be attacked by way of the blood-vessels 
of the choroid plexus. 

The changes observed consist of diffuse injection of the soft mem- 
branes, edema of the arachnoid, and a perivascular serofibrinous exudate 
along the course of the vessels coming from the veins. Microscopically, 
sections show around these vessels a mass of fibrin, in which are em- 
bedded a considerable number of polynuclear leukocytes. Often cells 
undergoing fatty degeneration are also found in these masses, lying close 
to the walls of the vessels in the portions of the brain where the changes 
are most pronounced. In this condition micro-organisms are usually 
found quite readily, either within or without the cells, those within the 
cells, in particular, frequently showing a partial loss of staining power 
that has been taken to indicate phagocytic activity. 

In the most severe cases the entire subarachnoidal space is dis- 
tended with a purulent accumulation. The surface of the brain can 
no longer be seen, the thick greenish exudate covering the convolutions 
as a smooth mantle. In nearly all these cases there is also pronounced 
edema, the arachnoid looking thick, shiny, and moist. Microscopical 
sections show the ordinary picture of a purulent accumulation; pus- 
cells in a fibrinous meshwork, desquamated endothelial cells, and micro- 
organisms. In all forms of acute leptomeningitis petechial hemorrhages 
into the arachnoid are common. The substance of the brain and cord 
may also be involved (meningo-encephalitis, meningomyelitis), and 



DISEASES OF THE BRAIN AND ITS MEMBRANES 877 

this involvement may vary from a slight increase of the neuroglia 
elements just beneath the pia to the presence of foci of round cells. 
These foci are usually found about the small vessels or lymphatics 
dipping in from the pia, the latter situation being by far the more fre- 
quent. Ordinarily they are microscopical and surrounded by a narrow 
zone of partially degenerated nervous substance, outside of which there 
is again a slight increase in the neuroglia tissue and cells. Occasionally, 
however, the cerebral involvement may be more extensive, and large 
abscesses are formed, leading to the destruction of considerable portions 
of the nervous substance. The nerve-fibers, even those in the neigh- 
borhood of the lesion, rarely show distinct alterations. The ganglion- 
cells, however, exhibit slight diffuseness in taking the stain, or irregulari- 
ties in the arrangement of the chromophilic bodies. If the abscesses 
are larger, either involving or close to the gray substance, the ganglion- 
cells may show extensive degeneration, with entire loss of staining power 
and fragmentation of the protoplasmic processes, nothing being left to 
indicate the position of the cells excepting an irregularly shaped vesicle 
containing some brownish pigment. These larger foci, however, are 
usually found in the white substance. 

An attempt has been made to distinguish varieties of meningitis 
according to the infective agents, and Netter has stated that in pneumo- 
coccic infection the pus is viscid and greenish ; in streptococcic infection, 
more serous and less adherent to the membranes. Influenzal meningitis 
is said to be commonly accompanied by pial hemorrhages and a peri- 
vascular infiltration extending rather deeply into the gray matter. 
Honl believes that only four forms can be differentiated — the thick, 
viscid pus of the pyogenic micro-organisms, the yellowish exudate of 
tuberculosis, the bluish-green pus of the Bacillus pyocyaneus, and the 
purulent exudate containing yellowish grains of actinomyces. 

Epidemic cerebrospinal meningitis does not differ essentially from 
the ordinary septic form, excepting in its cause, the meningitis coccus 
(q. v.). As a general rule, the inflammatory process begins upon the 
convexity of the frontal lobes, and proceeds backward and downward, 
the basal meninges being involved late in the course of the disease. 
Aside from those forms occurring as a complication of other pathological 
conditions that lead to death before the meningitis has been fully devel- 
oped, it is the one most likely to kill the patient before distinct altera- 
tions have become evident. These cases are spoken of as foudroyant or 
fulminant. The disease is often accompanied by lesions in other parts 
of the body, as petechia? in the skin, suppuration in the joints, multiple 
abscesses, endocarditis, degenerations of the myocardium, and suppura- 
tion of the labyrinth of the ear. 

Associated Changes. — Besides the meninges of the brain, those of 
the cord are almost always involved, even in cases of tuberculous 
meningitis. The peculiarities of these conditions are described in the 
section on the spinal cord. Extension along the fold of pia mater that 
covers the choroid plexus is also common. The cerebrospinal fluid 
may be turbid, there is a moderate amount of lymph on the ependyma 



878 



A TEXT-BOOK OF PATHOLOGY 



and over the surface of the plexus, and the latter may even contain 
small abscesses. Not infrequently, in prolonged cases, meningitic ad- 
hesions and occlusion of the aqueduct of Sylvius give rise to an acute 
hydrocephalus. 

Chronic leptomeningitis, a rare condition, may follow an acute 
attack or arise as a part of productive pachymeningitis or as a part of 
the chronic infections. It is commonly hypertrophic in form, leading to 
meningeal adhesions and involvement of the outer layers of the cerebral 
cortex in fibrous changes. The basilar form is perhaps the commonest, 
although a disseminated chronic meningomyelitis is usual in paresis. 

INFECTIOUS DISEASES 

Tuberculous meningitis is usually a manifestly secondary affection, 
although in children it may occasionally appear in connection with a few 
recent foci in other parts of the body. The bacilli ordinarily reach the 
meninges by the blood-vessels, particularly, in all probability, by the left 
carotid, from which situation they may spread along the base or to the 
vertex. Occasionally they seem to pass up the vertebral arteries, and may 
then affect the cerebellum more severely than the base of the cerebrum. 
Tuberculosis may also extend directly from tuberculous lesions of the 
skull or of the middle ear, and it has occasionally been observed to occur 
after traumatism. Other routes of infection, however, have been sug- 
gested, particularly, as in acute purulent meningitis, the organisms have 
been supposed to pass up the posterior mediastinum, the retropharyn- 
geal areolar tissue, and thence into the cranial cavity. Mixed infection 
not infrequently occurs, and has been supposed to account for the 
purulent exudate. It is certain, however, that pure tuberculous men- 
ingitis may at times occasion the formation of pus. The organism that 
is most frequently found in connection with tubercle bacillus is the 
pneumococcus, and it may be found intimately associated, although 
it has been stated that the tubercle bacillus appears to predominate 
at the base of the brain and the pneumococcus in the exudate of the 
convexity. 

Pathological Anatomy. — In cases that die of pulmonary tuberculosis 
it is not uncommon to find, particularly in the pia upon the convex- 
ity, a number of small grayish nodules. These are not always appar- 
ent upon superficial inspection, but by cutting through the cerebral 
hemisphere as far as the pia, and then stripping it away from the under 
surface of the membrane and holding the latter up to the light, they 
may readily be seen. In certain cases tubercle bacilli have been found 
when recognizable macroscopical lesions were entirely absent. Micro- 
scopical examination usually reveals a few masses of epithelioid cells 
and some slight perivascular round-cell infiltration. 

When the infection is more severe the tubercles are usually most 
numerous upon the base of the brain, particularly on either side of the 
carotid canal and in that part of the base just posterior to the dorsum 
sellse. Ordinarily the disease assumes the form of disseminated miliary 



DISEASES OP THE BRAIN AND ITS MEMBRANES 



879 



tuberculosis. The tubercles are situated between the arachnoid and the 
pia, often in the depths of the sulci. They vary in size up to 0.5 cm. 
in diameter, and often show slight cheesy degeneration in the center. 
The meninges are congested, and usually there is an exudate of inflam- 
matory liquid that contains flocculi of lymph, or is even seropurulent in 
character. Microscopical examination shows that the tubercles are 
composed of epithelioid cells, which occasionally seem to be dividing. 
Giant cells are also present, although perhaps not so frequently as in 
lesions in other parts of the body. There is usually round-cell infiltra- 
tion about the vessels, and the latter are apt to be distended. This 
round-cell infiltration may also extend into the cortex of the brain, and 
the tubercles are often found in the latter situation. Tubercles may also 
exist in the choroid plexus. Sometimes, if the process has lasted for 
some time and the tuberculous masses have increased in size, they may 
undergo cheesy degeneration and form irregular masses; these are 
usually found at the base of the brain, and often cause serious pressure 
upon the cranial nerves that they involve. 

Occasionally, when only a small number of bacilli have reached the 
meninges and have been deposited in one point, a single cheesy nodule 
may be found, particularly in one of the sulci, forming the meningeal 
tyroma, which sometimes attains a considerable size. In these less acute 
cases the exudate is considerable, and involves not only the subarach- 
noidal space, but also the ventricles of the brain, causing a condition 
that was formerly described as acute hydrocephalus. Numerous tubercles 
are found in the choroid plexus, and the ependyma is covered with slight 
elevations resembling somewhat the appearance of cor villosum. These 
are usually found to consist of proliferated epithelial cells and of the 
subependymal neuroglia and fibrous tissue. Tuberculous infiltration 
of the brain substance is, however, very common. This may be either 
nothing more than an extension by continuity along the lymph-spaces 
and blood-vessels dipping from the pia or ependyma into the brain 
substance, and giving rise to small foci composed of epithelioid and 
giant cells surrounded by leukocytes, and perhaps exhibiting a slight 
degree of cheesy degeneration in the center; or else considerable areas 
of softening, which are perhaps caused by the formation of thrombi. 
These are most frequent in the corpus striatum and the crura, and 
appear as grayish-white or yellowish areas of softened and degenerated 
nervous tissue. Not infrequently, punctiform hemorrhages are found 
in the cortex about these areas of softening. In general, extension of 
the tuberculous process to the meninges of the cord occurs if the duration 
of the process is at all prolonged, but the vertebral canal is so much longer 
than the spinal cord that pressure symptoms rarely occur, and, as the 
irritation is slight, the cranial symptoms dominate the clinical course. 

Syphilis may occur in the form of gummatous infiltration and 
diffuse inflammations. In the former instances there are found flat- 
tened nodular thickenings of the arachnoid and pia, of grayish or pink- 
ish color, and tending to undergo necrotic change. The process begins in 
the inner surface of the arachnoid, or sometimes in the walls of the blood- 



880 



A TEXT-BOOK OF PATHOLOGY 



vessels, and extends to the pia and cerebral substance on the one hand 
and to the dura on the other. In another form of syphilis there is diffuse 
infiltration or syphilitic leptomeningitis, causing considerable thicken- 
ing of the meninges. The characteristic of these conditions is the con- 
comitant obliterating endarteritis. The lesions of syphilis are like those 
of tuberculosis, but the endarteritis, periarteritis, and the characters 
of the giant cells help in the diagnosis. The syphilitic giant cells do not 
have the typical peripheral or polar nuclei. Nevertheless the diagnosis 
is often exceedingly difficult. 

Chronic syphilitic leptomeningitis and meningoencephalitis are 
occasionally met with. In these cases the membranes are thickened 




Fig. 421. — Gummatous meningoencephalitis (Ziegler). 



and fibrous, and secondary extension of the infiltration into the cerebral 
cortex occurs (Fig. 421). 

TUMORS 

The Pacchionian Bodies. — The most common, and clinically 
perhaps the least important, tumors of the arachnoid arise in the 
Pacchionian bodies. These are small granular masses or circumscribed 
nodules, chiefly along the edge of the superior longitudinal sinus, but 
often extending a short distance laterally over the convex surface of 
the convolutions. Microscopically they consist of dense masses of 
fibrous tissue, covered by a layer of proliferated endothelial cells, which 
give them a concentric structure. Occasionally some calcareous 
nodules may be found in them. They may undergo active hyperplasia 
and grow outwardly, frequently eroding the skull, and giving rise to 
little pits upon the inner surface. 

Endotheliomata are most frequently found in the pia mater. 
They are supposed to arise from the perivascular tissue or the arachnoid. 
They present irregular alveoli, lined with cuboidal or round endo- 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



881 



thelial cells. These are not always arranged in a single layer, but may 
occasionally fill the alveolus, although this is not common, and more 
frequently some have broken loose and lie free in the cavity. The 
cells often show karyokinetic changes, and occasionally alterations in 
shape, due to mutual pressure. These tumors resemble carcinomata 
closely, but the presence and proliferation of the epithelium-like cells 
in the stroma, such as occur in carcinoma, have not been observed 
(Fig. 422). They are soft gray or red, flat spreading masses. 

Sarcoma of the ordinary kinds may occur in the pia. Angiosarco- 
mata with and without degenerative changes are reported. Bone 
may be laid down in pial tumors (psammoma). Carcinoma does not 




Fig. 422. — Perithelioma of meninges. 



occur, but tumors resembling it will be discussed under ependyma 
and ventricles. 

Cholesteatomata are terata, and have been observed in two related 
forms: those consisting exclusively of squamous epithelial cells, and 
those containing, in addition, various other epidermal structures, such 
as hairs or sebaceous glands. They are usually situated in or about 
the median line of the calvarium; at the base of the brain; on the 
upper surface of the corpus callosum; or somewhere along the choroid 
plexuses. Those containing hair are most frequently found near the 
cerebellum, growing either from the arachnoid, or, more rarely, from the 
outer surface of the dura. Those arising from the dura may occur upon 
the frontal or occipital bones, and often show calcareous infiltration, 
or even true osseous formation. 

56 



882 



A TEXT-BOOK OF PATHOLOGY 



Lipomata are rare. They are usually found in children, and always 
in the soft membranes, especially the pia mater. The most frequent 
seats are the upper surface of the corpus callosum and the corpora 
candicantia. According to Bostroem, they are probably epidermal in 
origin, nothing but the subcutaneous fatty tissue being left. 

Teratomata. — Growths of more distinctly teratoid character 
than the cholesteatomata, above described, are occasionally found. 
Chiari has described a case that grew from the lining membrane of 
the third ventricle in an infant that died at the age of seven weeks. 
It consisted of a medullary white mass and a number of serous cysts. 
The solid substance was composed of fetal brain substance, in which 
were fissures lined with epithelium similar to that of the central canal 
of the cord, and ganglion-cells, retinal cells, skin-glands, and jelly of 
Wharton. Fibrous and cartilaginous tissues were also present. 

The Brain 
development and anatomy 

Development. — (For convenience, the development of the cord is considered 
in this place with that of the brain.) The central nervous system commences as a 
shallow depression, that appears in front of the primitive streak in early embryologic 
existence. It is bounded on either side by ridges, known as the medullary folds. 
The groove gradually becomes deeper, and finally the two medullary folds unite, 
giving rise to the formation of the medullary canal. The canal is first formed in the 
portion that subsequently forms the cervical region of the spinal cord. Just beneath 
the medullary canal there is a cylindrical collection of cells, often with a small cavity 
in the center that forms anteriorly a shallow groove, the so-called notochord. Its 
function is unknown, and it eventually disappears during embryonic existence. 
The anterior extremity of the embryo continues to grow, and bends downward, 
forming the cephalic fold. In this part of the neural canal three dilatations occur — 
the -primary vesicles of the brain; the posterior portion ultimately forms the spinal 
cord. 

The Cord. — At first the wall of the embryonal cord is composed of a single layer 
of cylindrical epithelial cells (spongioblasts), with nuclei at various distances from 
the central canal; these ultimately become the nuclei of the glia-cells. The central 
ends remain cylindrical; the peripheral ends become branched, forming the myelo- 
spongium, probably the antecedent of the neuroglia fibers, which, according to some 
investigations, become separated from the cells. At the age of about five weeks in 
the human embryo, certain cells, with a considerable amount of clear protoplasm, 
are found near the inner limiting membrane, the so-called germinal cells. Subse- 
quently other cells appear, probably derived from the germinal cells, as they are 
first found in the situations occupied by these, the so-called neuroblasts. These 
are distinguished by the appearance of a projection, pointing toward the periphery 
of the spinal cord, that grows out from the protoplasm and ultimately pierces the 
external limiting membrane to become an axis-cylinder. 

Just outside of the cord, probably from masses of epiblastic cells derived from 
its wall, the cells of the spinal ganglia appear. These are, at first, bipolar, one 
process extending into the spinal cord and the other peripherally, but ultimately 
the two processes unite at their commencement. The spinal cord at first com- 
pletely fills the spinal canal, but after the fourth month the vertebral column begins 
to grow somewhat more rapidly, and at birth the conus terminalis is opposite the 
third, and in the adult extends only to the lower end of the first, lumbar vertebra. 
The nerve-fibers are at first non-medullated, but later myelin-sheaths appear, first 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



883 



in certain parts of the posterior columns, and lastly in the pyramidal tracts, which 
often, at birth, are not yet entirely medullated. The membranes are derived from 
the mesoblast. 

The Brain. — The three primary vesicles from which the brain is developed con- 
tinue to grow, and the first is subdivided by a median constriction into two secondary 
vesicles, the prosencephalon and the thalamencephalon. From the former two 
lateral offshoots appear, which give rise to the cavities of the lateral ventricle, and 
from the walls of these are developed the cerebral hemispheres, the olfactory lobes, 
and the corpus callosum. The cavity of the second vesicle forms the third ventricle, 
and from its walls grow the nervous structures of the eye, the optic thalami, and the 
pituitary and pineal bodies. The cavity of this vesicle (mesencephalon) forms the 
aqueduct of Sylvius, and from its walls grow the corpora quadrigemina and the 
crura. The posterior primary vesicle also becomes constricted, forming the epen- 
cephalon and the metencephalon. The two cavities, however, remain united and 
form the fourth ventricle. From the walls of the anterior portion are developed the 
cerebellum and the pons. From those of the posterior portion, the medulla oblongata. 

The ultimate shape of the brain, however, is largely determined by certain flexures 
and by the growth and extension of the axis-cylinders, which pass in various direc- 
tions and form the white matter, the greater bulk of the central nervous system. 
Differing from the cord, the growth of the brain exceeds that of its containing bony 
capsule. As a result the surface of the hemispheres is usually thrown into folds. 
The earliest of these appear during the third month, and are usually transverse to 
the axis of the brain, although not invariably. The lateral ventricles at this stage 
are very large, and the sulci project into their cavities as ridges. During the fourth 
month the deep fissures disappear, with the exception of three — the Sylvian, the 
calcarine, and the parieto-occipital fissures. The hippocampal fissure also appears 
about this time. The other permanent sulci appear about the end of the fifth month, 
the earliest being the fissure of Rolando; but many of the secondary fissures do not 
develop until after birth. 

The sympathetic nervous system is probably only an offshoot of the central 
nervous system. The cells first appear upon the spinal nerves, from which they 
wander, remaining connected with them by short branches, the rami communi- 
cantes. Some authorities, however, believe that the sympathetic system is devel- 
oped from the mesoblast. 

Anatomy. — The brain consists of the two cerebral hemispheres, the basal ganglia, 
the pons, the medulla, and the cerebellum. Its weight varies from 1200 to 1300 
grams in the adult female, and from 1300 to 1400 grams in the adult male. Its 
consistency at birth is very soft; in the adult it becomes somewhat firmer, but is 
always softer than the normal liver. Its color varies from grayish white in the parts 
composed of medullated fibers to reddish gray in those composed chiefly of ganglion- 
cells. The cerebral hemispheres are separated by the superior longitudinal fissure, 
and united by the corpus callosum and the anterior commissure. They are joined 
to the pons by the crura. Their surfaces are rendered very irregular by the presence 
of numerous fissures or sulci, and are divided into the frontal, parietal, occipital, and 
temporosphenoidal regions. The important fissures are the Sylvian, the Rolandic, 
and the parieto-occipital on the external surface; the calloso-marginal, the calcarine, 
and the parieto-occipital on the medium surface. 

The hemispheres are composed essentially of an outer layer of gray matter, the 
cortex, containing ganglion-cells, and of fibers passing from these in various direc- 
tions and uniting them with other parts of the central nervous system. These may 
be divided into three main classes: the projection fibers, passing between the cortex 
and the basal ganglia, or into the internal capsule; the transverse or commissural fibers, 
passing between the two hemispheres; and the association fibers, passing between 
different areas in the same hemisphere. The most important clinically of the pro- 
jection fibers are those which arise in the motor portion of the cortex, and pass first 
into the internal capsule, where they are grouped about the knee, thence through 
the crura and the pons, to form ultimately the pyramids of the medulla. They 
decussate in the first cervical segment of the cord and form the pyramidal columns of 



884 



A TEXT-BOOK OF PATHOLOGY 



the cord. The fibers of the optic radiation commence in the cortex about the cal- 
carine fissure and in the cuneate lobe, and pass forward to the pulvinar of the optic 
thalami. They are also associated with the external geniculate body and the ante- 
rior corpus quadrigeminus. From the pulvinar, the optic tracts pass around the 
crusta, then lie below and to the inner side of the internal capsules, and unite in 
front of the tuber cinereum to form the chiasm from which the optic nerves arise. 

The transverse or commissure fibers include those of the corpus callosum and of 
the anterior commissure. The fibers in the corpus callosum appear to correspond 
closely to those regions of the brain situated nearest to them. The anterior com- 
missure is composed of fibers uniting the temporosphenoidal lobes of the two 
hemispheres. 

The association fibers either connect adjacent lobes (fibres proprice), or unite dis- 
tant portions of the hemispheres (the long association fibers). 

In the substance of each hemisphere are found the lateral ventricles: two long, 
narrow, branching cavities, joined to the third ventricle by the foramen of Monro. 
Each contains a choroid plexus, and is normally lined with epithelium and contains 
clear cerebrospinal fluid. The anterior portion of the two ventricles is separated by 
the septum. A small double layer of epithelial cells line and almost fill the cavity 
of the third ventricle. The basal ganglia of the brain are the lenticular nucleus, the 
caudate nucleus, forming together the corpus striatum, and lying on either side 
outside of the internal capsules, the optic thalamus, a large oval mass lying beneath 
the caudate nucleus. To the outer side of the lenticulate nucleus is a band of white 
fibers, known as the external capsule, that is separated from the cortex by a thin layer 
of pigmented cells, the claustrum. 

The third ventricle communicates with the fourth by a narrow canal, the aque- 
duct of Sylvius, which passes through the tegmentum of the crura. It is surrounded 
by a zone of gray matter, in which are found the nuclei of the oculomotor nerves. 
Above it are the four corpora quadrigemina, two pairs of rounded eminences with a 
white cortex and a gray center. The superior corpora, as has been already stated, 
are intimately connected with the optic tract. Just anterior to these bodies is the 
small pineal gland, situated above the posterior commissure. Externally to the 
crura on either side, continuous with the posterior portion of the thalamus, are the 
two geniculate bodies, separated by the optic tract. The optic thalami lie on either 
side of the third ventricle and just beneath the caudate nuclei ; they are oval bodies 
containing numerous groups of nerve-cells, the anterior portion being called the ante- 
rior tubercle, and the posterior portion the pulvinar. 

The two great channels by which fibers pass to and from the cerebrum are the 
crura cerebri. These are divided by a narrow layer of dark-gray material, the sub- 
stantia nigra, composed of pigmented ganglion-cells, into the crusta or inferior por- 
tion, and the tegmentum or superior portion. A part of the crus is formed, as has 
already been stated, by the pyramidal tract. Sensory nerve-fibers are found in two 
groups in the tegmentum toward the outer edge, comprising the inferior and superior 
fillets. 

The two crura unite to form the pons, which is composed, ventrally, of bundles 
of motor fibers separated by the commissural fibers of the cerebellum, and dorsally, 
partly of the fibers of the fillet and partly of gray matter. Below the pons is found 
the medulla, which is really nothing but the upper portion of the spinal cord. Ante- 
riorly we find two well-defined bundles of motor fibers, the pyramids; just back of these 
the lower olives; and on the dorsal surface the nuclei of the tenth and twelfth nerves, 
and externally to them the nucleus gracilis and nucleus cuneatus, the terminations 
respectively of the columns of Goll and Burdach of the cord. The axis-cylinders 
of the cells that compose these nuclei pass toward the brain and form the fillets. On 
the outer surface of the medulla, near the dorsal surface, are the two restiform bodies, 
the continuations' of the cerebellar peduncles. 

The cerebellum is composed of two lobes and the vermiform process. Upon 
cross-section it is seen to be composed of a great number of narrow gyri separated 
by deep ramifying sulci, each convolution being lined externally by medullated 
fibers, beneath which is a layer of ganglion-cells enclosing a center of medullated 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



885 



fibers. It is united to the cerebrum by the superior peduncles, which terminate in 
the nucleus ruber of the tegmentum. The middle peduncles form the transverse 
fibers in the pons, and the inferior peduncles pass into the restiform bodies of the 
medulla. Certain nuclei are found in the interior of the white substance, of which 
the most important is the dentate nucleus, analogous structurally to the olives of 
the medulla. 

The Neuron. — Histologically, the essential element of the nervous system is the 
neuron. This, in the sense of Waldeyer, comprises the nerve-cell, its protoplasmic 
processes (which are branched), and the axis-cylinder, or axone, which may be a 
single fiber giving off angular collaterals, or is extensively branched (Golgi cells). 
The cell-body consists of protoplasm without a distinct cell wall, and containing or 
not containing chromophilic bodies. According to Nissl, two groups of cells are thus 
formed, the somatochromes with, and the caryoehromes without, these bodies. 
According to zoologists, these are respectively motor and sensory in function, but the 
cells of the spinal ganglia, which appear to be sensory, contain these granulations. 
Cells are spoken of as multipolar or bipolar, according to the number of processes 
that project from them. It is impossible to describe in this place all the varieties 
of cells and their distribution in the nerve substance. The neurons may be divided 
into endogenic, wholly within the central nervous system, and exogenic, partly in 
the peripheral nervous system. Each axis-cylinder terminates in a tuft of fibers that 
surround, without touching, some other ganglion-cell, or, if it extends to the periphery, 
terminates in a special sensory corpuscle or a muscle-plate. Upon emerging from a 
cell the axis-cylinder becomes surrounded by a sheath of myelin, while about several 
axones and their covering a fibrous coating, the sheath of Schwann, appears. 

Nerve-cells and fibers are supported by a special tissue, glia-cells and their inter- 
lacing fibrils. The cells are small, deeply staining, and of round or irregular shapes, 
beset with numerous delicate branches. In the white matter these cells are called 
"spider cells," and have stiff straight processes, while in the gray matter the branches 
are more irregular and are subdivided. There is beside these cells a small amount 
of ordinary connective tissue. 

Physiology of the Brain. — This subject can be touched upon only very briefly. The 
brain is the organ in which all the intellectual processes are performed, but it is as yet 
unknown how this is accomplished. A number of theories have been suggested, but 
none of them are based upon observed fact. We are better informed concerning the ori- 
gin of certain specific motor impulses in the brain, and the regions where stimuli from 
certain of the special sense organs are received. The motor region is situated in the 
two gyri on either side of the fissure of Rolando, and in the posterior portions of the 
three frontal gyri. In general, it can be said that the centers are arranged so that 
the cells sending fibers to the highest portion of the body — that is, the face, eyes, 
etc. — are situated in the lowest portion of the motor region; and the cells sending 
impulses to the lowest portion of the body — the feet, for instance — are situated in 
the highest portion of the motor region along the superior longitudinal fissure. 
This region has been mapped out by the aid of direct observation, not only upon the 
lower animals but upon human beings. Any irritation causes movement of the 
corresponding portion of the body, the movement being of a co-ordinated and not 
of an individual muscular type; that is to say, the stimulation of a center in this 
region causes contraction of a number of muscles, with the object of accomplishing 
some definite movement. The fibers of the motor region constitute the pyramidal 
tract, whose course has already been described. Irritative lesions of the motor cortex 
produce convulsive explosions, clonic in type, usually described as epileptic. If the 
lesions are sharply circumscribed, and the convulsions occur always in a certain defi- 
nite group of muscles, the condition is spoken of as Jacksonian epilepsy. Destructive 
lesions cause paralysis of a spastic type; that is to say, the lower motor neurons 
evidently suffice to maintain a condition of contractility in the muscles, which may 
be exalted either as a result of some irritation exerted by the degenerated central 
motor neurons, or because, under normal conditions, the central motor neurons 
exert an inhibitory or restraining action. We are still in ignorance concerning the 
localization of the sensory impulses. The effect of lesions in the upper portion of 



886 



A TEXT-BOOK OF PATHOLOGY 



the parietal lobe in producing sensory forms of muscular inco-ordination has led 
to the supposition that the fibers conveying muscular sense terminate in this region. 
It is practically certain that the great majority of the sensory fibers terminate in the 
optic thalamus, from which other fibers proceed to the cortex; but as brain physiol- 
ogists are practically agreed that all the active intellectual processes are accomplished 
in the cortex, it is supposed that the thalamus is merely a situation in which some 
alteration or modification of the impulses received from the periphery occurs. Regard- 
ing the special senses, the visual impressions terminate in the cuneus. The auditory 
centers are situated in the superior temporosphenoidal convolutions, and the destruc- 
tion of these centers produces loss of understanding of sounds heard — that is to say, 
sensory aphasia. The centers for olfaction are situated in the uncinate gyri. Irri- 
tation of these regions has in some cases apparently given rise to subjective odors, 
usually disagreeable. They may occur as the aurse of epileptic attacks. The center 
for taste has not been located, although it is probably in this region. The func- 
tions of the remaining portions of the cortex are practically unknown. It is supposed 
that the intellectual processes are performed chiefly in the frontal lobes. At any 
rate, extensive lesions of these lobes have caused alterations in character — loss of the 
faculty of attention, more or less stupidity, and hebetude. Occasionally ataxia is 
present. The relation of pathological processes in the brain to insanity is not well 
determined. Lesions have, of course, been found in paretic dementia, in acute deli- 
rium, and in idiocy, but examination of the brain in cases of paranoia and melan- 
cholia has been practically negative. The functions of the other portions of the brain 
are not well determined. The basal ganglia are apparently merely stations in the 
paths of the fibers, chiefly those of sensory nature. The anterior corpora quadri- 
gemina have something to do with the fibers of the optic tract, and in them is prob- 
ably situated the center of the pupillary reflex to light. The external geniculate 
ganglia are apparently associated with the fibers conveying auditory impressions. 
The pons contains the ganglion-cells of the peripheral motor neurons of the eye- 
muscles, but is otherwise merely a pathway for various tracts of fibers. The medulla 
contains the ganglion-cells of the cranial nerves, and, in addition, all the tracts of 
fibers passing between the brain and cord. The functions of the cerebellum are not 
well known. There is no doubt that it has something to do with equilibration, but 
the lesions must be situated either in the vermis or bilaterally. 

POSTMORTEM DEGENERATIVE CONDITIONS 

It is important to be acquainted with the postmortem alterations that may take 
place in the nervous system, in order to avoid the confusion of such changes with 
those that have occurred as the result of disease. Little attention has been paid to 
the macroscopical changes, and they are not characteristic. Their degree depends 
upon the temperature at which the body has been kept after death, the nature of the 
disease that preceded death, and the period that elapsed before the tissues are 
removed. Ordinarily no changes will be noticed under thirty-six hours if the body 
is kept on ice. If kept at a temperature of about 16° C. (61° F.), the brain and cord 
will appear normal if removed within twenty-four hours. There is first softening of 
the nervous tissue that is general and not associated with pigmentation; the tissues 
may become so soft that it is almost impossible to remove them without injury. 
Later, there is often a considerable extravasation of blood-pigment around the 
vessels; and, finally, if putrefaction is advanced, the tissues become almost difHuent 
and light brown in color. 

Italian authors have studied methodically the microscopical changes. The nerve- 
cells swell, their protoplasmic processes break off, and there is a gradual loss of the 
staining power of the chromatin bodies; vacuoles appear in the protoplasm and the 
outline of the cell becomes irregular, and finally the chromatin substance completely 
disappears. The outlines of the nucleus become indistinct, it swells, and then con- 
tracts, with irregularity of the outline. It stains homogeneously, due to diffusion 
of the chromatin, and may contain small granules of hyaline material. Later it 
loses its staining power, and finally disappears completely. The nucleolus is the 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



887 



last structure to show alteration; it may swell slightly, become filled with vacuoles, 
and then break up into granular material and disappear. The protoplasmic processes 
do not exhibit varicosities, but apparently become more fragile, and are very apt to 
be broken off during staining. Changes may take place in the myelin-sheaths that, 
when studied by Marchi's method, are not greatly different from those seen in areas 
of softening — that is, small fatty granules appear along the course of the nerve-fiber. 
In postmortem lesions there is no perivascular round-cell infiltration; no compound 
granular cells can be found in the tissue; there are no signs of proliferation in the 
neuroglia, and the process is more general and uniform than is apt to be the case in 
morbid conditions. 

CONGENITAL ABNORMALITIES 

The deformities of the brain are numerous and complicated. They 
may be divided roughly into those associated with alterations in the 
skull and those occurring within the cranial cavity. 

Acrania is a deformity characterized by absence of the skull. The 
membranes are usually preserved and form a sac filled with serum, on 



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Fig. 423. — Meningo-encephaloma which grew in a meningocele into the nose. Note the 
cerebral, meningeal, and glial elements. 

the inner surface of which small particles of nervous tissue may occa- 
sionally be found. More frequently the brain forms only a small mass 
at the upper portion of the spinal canal, lying on the basilar process 



888 



A TEXT-BOOK OF PATHOLOGY 



of the occipital bone. Sometimes it appears as if the sac had ruptured 
or had never completely closed, for the membranes are collapsed and 
form upon the base of the skull a mass consisting of fibrous connective 
tissue and blood-vessels. Often in this case the encephalon is entirely 
absent, but the pons and medulla may be almost completely developed. 
The cranial nerves are present. 

Hemicrania is a condition in which more or less of one of the parietal 
bones, or of a portion of the frontal or temporal bone, has failed to 
develop. The corresponding portions upon the opposite side that have 
developed are usually hypoplastic. Ordinarily, anencephaly, or else 
partial development of the brain, is associated with these changes. 

Cranioschisis is the name applied to imperfect closure of the 
skull along the middle line. This may be associated with rhachischisis, 
in which case both skull and spine are cleft. The commonest situations 
for small fissures are in the frontal bone, in the region of the posterior 
fontanel, in the median line of the posterior portion of the occipital 
bone, and, more rarely, in the region of the anterior fontanel or the 
sagittal suture, or in the sphenoid bone. 

Fissures or other small defects usually occasion hernia of the brain, 
which is named encephalocele, and according to its situation anterior 
or posterior, frontal or occipital, superior, inferior, or lateral. If, instead 
of brain substance, only the membranes protrude through the fissure, 
the condition is known as meningocele. In these cases the cavity is 
filled with cerebrospinal fluid. Sometimes the under surface of the 
membrane is lined with nervous tissue, showing that it represents a 
dilatation of one of the primary cavities of the brain, corresponding to 
the condition found in spina bifida. These congenital hernia? are prob- 
ably the result of fetal hydrocephalus, although it is possible that the 
chief cause is the imperfect development of the cranium. In cases in 
which the fissure is in the sphenoid bone, it is not uncommon to find, 
as an associated condition, cleft palate. Life is, of course, incompatible 
with extensive encephalocele. If it is small, the neck of the sac is some- 
times constricted, either spontaneously or as a result of surgical inter- 
ference, and recovery ensues. 

Cyclencephaly is a peculiar deformity in which there is failure 
of the anterior cerebral vesicle to develop. The frontal lobes remain 
fused and one rudimentary central eye develops (cyclopia). 

Abnormalities in Size. — The size of the brain is subject to con- 
siderable variation. 

Macrocephaly is the condition in which the brain is excessively 
large — that is, more than 1500 gm. This may be of two kinds. In 
the first, and perhaps less common, form the brain is entirely normal 
in structure, the proportion between the various parts being maintained 
and the relation between the nervous tissue and the neuroglia not altered. 
In some instances the subjects possess unusual intelligence; in others 
this is not the case. The second form is enlargement of the brain with 
hyperplasia of the neurogliar tissue. This is not infrequently found in 
the so-called hypertrophic nodular gliosis. In this condition the brain 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



889 



may be considerably enlarged, and the convolutions may be increased 
in size, although not abnormal in arrangement. Microscopically, the 
changes described in the section on sclerosis are discovered. A pseudo- 
enlargement of the brain is produced by hydrocephalus. The weight of 
the brain, after the liquid has been removed from the cavities, is usually 
less than normal, although this is not always the case. 

Hypertrophy of the brain may be. limited to certain parts. These 
are usually individual gyri, and are nearly always sclerotic. Sometimes 
only a portion of a convolution is thus affected, and produces a tumor- 
like swelling. Hypertrophy of individual sections of the encephalon, 
such as simple enlargement of the cerebellum, or of one of the cerebral 
hemispheres, does not appear to have been observed. 

Microcephaly is a condition in which the brain is much smaller than 
normal, as a result of defective growth cr early fusion of the skull bones 
limiting the development of the encephalon, or else of disease, either in 
early life or later. In some instances the brains, aside from their small- 
ness, appear perfectly normal, and this diminution in size, within certain 
limits, is not incompatible with normal intelligence. Usually, however, 
there are sclerosis and decrease in size of some of the gyri. There are, 
of course, the associated changes usually found in sclerotic conditions. 

Hypoplasia of individual portions of the brain has been observed, 
particularly of the corpus callosum, the cerebral hemispheres, and the 
cerebellum. 

Hypoplasia of the cerebral hemispheres is usually due to some path- 
ological change, and will be discussed under sclerosis and porencephaly. 

The congenital absence, either total or partial, of the corpus callo- 
sum has been observed in a number of cases. It may occur in brains 
otherwise normal, but is usually associated with microcephaly or other 
profound structural changes. In the cases in which no other lesions 
exist the intelligence may be normal, but in the great majority of in- 
stances the patients are idiots. The appearance of the brain is quite 
characteristic. As soon as it is removed the hemispheres fall widely 
apart, showing the third ventricle covered with a delicate layer of pia 
mater. The inner surfaces of both hemispheres are divided by numer- 
ous fissures, and appear atypical. In cases of marked hydrocephalus 
the corpus callosum is extremely thin, and may be torn during the 
removal of the brain, and this may possibly be mistaken for congenital 
absence. A careful examination, however, will usually reveal the true 
state of affairs. 

Hypoplasia of the cerebellum, or even total absence of one or both 
hemispheres, has been occasionally observed. It is nearly always 
associated with sclerosis. A collection of cerebrospinal fluid in part 
supplies the place of the absent organ. The cerebellum may be of 
normal shape, and even microscopically show no changes other than 
diminution in size. More commonly, however, the changes are asym- 
metrical, one lobe being markedly smaller than the other, and perhaps 
reduced even to a small papilla. There are often sclerotic changes, 
with marked atrophy of the cortex and disappearance of many of the 



890 



A TEXT-BOOK OF PATHOLOGY 



medullated fibers. The corpora quadrigemina may also be altered, 
but this is not invariably the case. 

Other changes of unknown significance that have been described are 
abnormal arrangement of the convolutions. Of these the most important 
is the presence of annectant gyri across the Rolandic fissure, or the 
absence of annectant gyri in the parieto-occipital fissure. It does not 
appear, however, although the claim has been frequently made, that 
these changes are in any way associated with intellectual peculiarities. 
Bundles of nerve-fibers, taking an abnormal course, have occasionally 
been found in the pons and medulla. These seem to be produced by 
premature decussation of portions of the pyramidal tract, and are of no 
clinical significance. 

Anencephaly, or total absence of brain, is a congenital lesion 
usually associated with acrania. Sometimes it is associated with total 
absence of the spinal cord; in other cases a portion of the pons, medulla, 
and the cord are still present, although much smaller than normal. 
The cranial nerves are usually present, and the eyes, in particular, are 
nearly always perfectly developed. The lesion is, of course, incompat- 
ible with life, although when the medulla is present a few respirations 
may take place after birth. The appearance of the monsters is very 
characteristic. From the orbital ridge of the frontal bone the skull 
slopes in almost a direct line to the neck, making the face and eyes un- 
usually prominent — the so-called frog-face. Frequently other deformi- 
ties are also present. 

Porencephaly is a condition characterized by the absence of a 
greater or less amount of the substance of one or both of the cerebral 
hemispheres, leading to the formation of a cavity or cavities filled with 
cerebrospinal fluid. 

Etiology. — The cause of porencephaly is not definitely known. As 
Von Kahlden remarks, the similarity of the lesions in typical cases is 
such that it seems reasonable to accept a uniform etiology. Kundrat 
believed that the lesions were due to anemic infarction, as a result of 
occlusion of the Sylvian arteries. Von Kahlden, however, believes 
that it is the result of some disturbance in a development of the brain, 
and bases his opinion upon the symmetry of the lesions and their pecu- 
liar situation. Other authors have suggested an inflammatory origin 
of the process, because of the adhesions between the membranes. 
Some cases seem to be due to a failure of blood-supply to the affected 
part, either by malformation of the vascular channels or endarteritis. 
A certain number of cases certainly develop after birth; these may be 
due to injury, such as might be produced by instrumental delivery, or 
by blows upon the skull, or by embolic or inflammatory processes. 

Pathological Anatomy. — Von Kahlden has divided a large series of 
reported cases into two classes : the typical and the atypical. The former 
class comprises about two-thirds of all the cases, and is characterized 
by the presence of a funnel-like cavity in the motor region of the brain, 
usually bilateral, although unequal, that extends from the subarachnoid 
space to the cavity of the ventricle (Fig. 424). Frequently this condi- 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



891 



tion is associated with imperfect development or exposure of the island 
of Reil. In the atypical form the lesions are exceedingly various; 
they may be found in any part of the cerebral hemispheres; the shape 
of the cavity may be either a shallow depression or a deeper loss of 
substance. Often — in fact, usually — there is no communication between 
the cavity and the ventricle. These varieties may even be found in the 
cerebellum, and perhaps are most frequent in the lateral lobes at the 
point where they unite with the vermiform process. Cases have also 
been recorded with cavity formation in the base of the brain, communi- 
cating sometimes with one of the horns of the lateral ventricles. A sort 
of cystic formation has been described, in which multiple cavities, not 
communicating with either the ventricle or subarachnoid space, have 
been found in the substance of the brain. The macroscopical changes 
observed in the typical form are as follows : Ordinarily a distinct depres- 
sion is noticed in the dura after the skull has been removed; when this 
region is more carefully examined it is found that the dura may or may 
not be adherent to the arachnoid which covers the cavity. The pia 
usually dips into and covers the excavation, and may be continuous with 
the ependyma of the ventricle. The adjacent convolutions of the brain 
are arranged in a somewhat radiate 
manner and turn down into the cavity, 
although this is not invariably the case, 
for they sometimes may appear as if 
simply cut off, being otherwise normally 
arranged. Associated changes in the 
brain are microgyria ; proliferation of the 
neuroglia tissue, and perhaps also of the 
connective tissue; atrophy of the nerve- 
cells in the cortex, particularly of the 
large pyramidal cells; and more or less 
complete destruction of the nerve-fibers 
in the region adjacent to the defect. 
The spinal cord usually exhibits a sec- 
ondary degeneration in the pyramidal Kg. 424.— Porencephaly (case of Dr. 
columns; this, however, is not always 

the case, for sometimes it appears that one or both pyramidal columns 
have failed entirely to develop, giving rise to a condition of micromyelia. 
Other parts of the brain appear to be rarely affected in the typical form 
of the condition. When the lesion is situated in any other part than 
the central region, corresponding secondary degenerations may, of 
course, occur. 

GENERAL PATHOLOGIC ANATOMY OF THE NERVOUS SYSTEM 

The pathology of the nervous system differs from that of the other 
organs of the body chiefly in the fact that the special structure of which 
the nervous tissue is composed have no close analogies to the epithelial 
and connective tissues. It is desirable, therefore, to discuss first the gen- 
eral changes occurring in the nerve-cells, nerve-fibers, and the neuroglia. 




892 



A TEXT-BOOK OF PATHOLOGY 



The Nerve-cell 

On account of their characteristic appearance and sharply differ- 
entiated structure, the cells of the anterior cornua of the spinal cord 
have been most carefully studied, and it is necessary, therefore, that we 
should give a brief description of their anatomy. The appearance 
depends largely upon the method of staining employed. By the Golgi 
method the cell appears as an irregular body, from which come a number 
of thick processes that rapidly divide and subdivide until they appear 
as a maze of independent delicate branches, dendrites, upon either side 
of which can be seen minute projections, the so-called gemmules; from 
one portion of this cell a fine process arises that is of uniform width, the 
neuraxon. At regular intervals this gives off the so-called collaterals, 
delicate branches that spring from it at right angles and have a different 
course. By this method other ganglion-cells in the nervous system have 
also been carefully studied and show numerous variations in type, the 
most important being in the number and complexity of the protoplasmic 
processes, and the division or even excessive branching of the neuraxon. 
The morbid changes that can be observed by the application of this 
stain are but few, since it appears that the pathological cells soon lose 
their power of impregnation. 

Apathy and Bethe, by the employment of certain exceedingly com- 
plex staining methods, claimed to have discovered that the nerve- 
cells are really nothing but stations in the paths of certain delicate 
fibrilla, called the neuro-fibrils, that pass from one cell to another, not 
being limited even to the ganglion-cells, but also passing through the 
neuroglia cells. They therefore believed, and Nissl has agreed with 
them, that these fibrils are the real functioning elements in the central 
nervous system, and that the ganglion-cells have probably only some 
nutritive influence. 

The alterations of the dendrites are essentially of two kinds: first, 
the appearance of varicosities upon the protoplasmic processes in their 
thicker branches; second, the disappearance of the gemmules from the 
terminal filaments. Such alterations have been seen in chorea, in gen- 
eral paresis, in alcoholism, and other forms of poisoning. Sailer found 
very marked changes of this character in the spinal cords of guinea- 
pigs killed with tetanus toxin, and Steele described a varicosity upon 
the axis-cylinder in the cortical cell in an animal killed by diphthe- 
ria toxin. Lenhossek appears to regard the varicosities of the proto- 
plasmic processes as the result of an accumulation of the ehromophilic 
bodies, and Kolliker states that they are merely artefacts, a view held 
by most zoologists. 

In 1885 Nissl described a method for staining the nerve-cells which, 
on account of its differentiation of the structures of the protoplasm, 
and the possibility that by it cells in any stage of degeneration may be 
stained, has yielded most valuable results. It consists essentially of 
staining tissue, hardened in alcohol, by one of the basic anilin-stains, 
such as thionin or methylene-blue. The cells of the anterior cornua 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



893 



show the irregular outline and the numerous protoplasmic processes 
as before. Throughout the protoplasm are small, irregular bodies, 
sometimes vacuolated, that take the basic stain intensely. They are 
arranged somewhat concentrically around the nucleus, but at the 
points where the protoplasmic processes come off become spindle shaped 
and turn into them, and are also found in the processes as spindles. 
Between these bodies the cytoplasm refuses to take the stain, and 
is called the achromatic substance. Nissl and some others believe that 
it has a delicate fibrillar structure, but this has not been positively 
determined. A cup-shaped portion of the protoplasm remains clear, 
and is usually rather sharply delimited from the remainder of the cell. 
From this extends a long, faintly staining, undifferentiated neuraxon. 
The nucleus does not stain, but remains as a clear space near the center 
of the cell, containing a round deeply staining and usually vacuolated 
nucleolus, surrounded by a membrane with irregular thickenings (Fig. 
425). It has been claimed (Kronthal) that these so-called chromophilic 




Fig. 425. — Normal and degenerated nerve-cells of the anterior cornua of the spinal cord; 

X 600. 

bodies do not exist in the living cell, but are the products of disinte- 
gration. The course of pathological changes appears to be somewhat 
as follows: The granules become first very irregular in distribution and 
somewhat finer, so that the concentric arrangement is no longer dis- 
tinct. They may then diminish considerably in number, so that the 
cell as a whole appears very much paler; finally, the protoplasm may 
become entirely clear, a small amount of basophilic substance only 
remaining that is collected in irregular masses around the nucleus. 
This also may disappear, and the cell remain as an irregular, faintly 
and diffusely stained mass in the midst of the tissue. This series of 
changes is by no means the only one that has been described. Occa- 
sionally the chromophilic granules seem to dissolve, although their 
capacity for staining is unimpaired, resulting in deeply and diffusely 
staining cells without any apparent structure, excepting the vesicle 
in the situation of the nucleus {'pyknomor-phous state). Nissl regards 
these as artefacts, and it is true that they are frequently found in tissues 
supposed to be healthy. It must not be forgotten that they are always 



894 



A TEXT-BOOK OF PATHOLOGY 



far more numerous in diseased tissues or in the neighborhood of 
focal lesions. We have observed some singularly beautiful examples 
of this change in the brain of a guinea-pig killed by anthrax, in which 
the micro-organisms were found in the nervous tissue. The solution, 
with or without loss of staining power, corresponds very closely to the 
changes observed in the chromatin in karyolysis, and may be very 
properly described as a sort of chromolysis. In other cases chromo- 
philic bodies may collect in diffuse, irregular masses in one or more parts 
of the protoplasm, a change which has been observed in the spinal cells 
of cases of tetanus. 

Still another form is the coalescence of the chromophilic bodies, so 
that each individual one appears larger; their number is less, and they 
still maintain a rather regular arrangement in the protoplasm. These 
masses may then further coalesce, giving rise to the appearance just 

previously described, or may break up, 
|H , . causing a uniform granulation of the 

. * i; 9 ^ ,* Jill cell, or they may disappear. Berger has 
attempted to explain most of these phe- 
nomena by supposing that the chromo- 
philic bodies are really composed of 
small granules that are adherent to the 
sides of the spaces formed by the retic- 
ulum of the protoplasm of the cell. If 
these spaces dilate, the granules will be 
more widely separated and the appear- 
ance will be that of diffuse granulation. If 
they contract, as occurs in cases of general 
cellular contraction or so-called inspis- 
sation of the cell, they will appear darker 

Fie. 426. — Degenerated nerve- 1,1 • ir • 7 j. 

cells in the neighborhood of a collec- and the neighboring ones may seem to 
tion of pus; the granular appearance coalesce. The changes in the reticu- 

is due to an excess of pigment; X 600 , 1 1 i 1 • 1 1 

(case of Lloyd and Sailer). him may be local, and give rise to local 

alteration in the arrangement (Fig. 426). 
Another change that frequently occurs in pathological cells is 
vacuolization. It is possible that a few vacuoles of small size may be 
the result of the hardening processes. In some cases, however, this 
alteration is very extensive, the vacuoles reaching 70 /x in diameter. 
They appear to be filled with a liquid, possibly lymph, that may undergo 
slight coagulation-necrosis; at least fibrillar, that may be fibrin, have been 
observed. The cells often acquire extraordinary appearances. Indeed, 
it may look as if the pericellular space was enormously dilated, and that 
bands of protoplasm extended from it to the surrounding neuroglia. 
The arrangement of the vacuoles is always exceedingly irregular, and 
if more than one be present, as is usually the case, the vacuoles vary 
greatly in size. 

Sometimes, instead of the vacuoles, there may be found in the cells 
masses of some substance that differs from the protoplasm. These 
are usually homogeneous irregular masses that take the acid stain, and 




DISEASES OF THE BRAIN AND ITS MEMBRANES 



895 



have been described as "colloid" in nature, using the word in the sense 
given it to by von Recklinghausen. The true nature of this change, 
however, is not very clearly understood. Sometimes the vacuoles 
appear to be replaced by clefts distributed irregularly in the proto- 
plasm. 

In nearly all degenerated cells there is accumulation of a peculiar 
cellular pigment. This may be fatty in nature, as it stains black with 
osmic acid. In some cases it seems to increase pari passu with the dis- 
appearance of the chromophilic bodies, so that ultimately the cell 
appears as an irregular mass filled with this yellowish-brown pigment. 
It occurs normally in old age, is found in the cells of the substantia 
nigra of the crura, is an almost invariable accompaniment of those 
diseases in which a sort of early senility appears to occur, such as general 
paralysis, and is rarely found in cells undergoing very acute degenera- 
tion. Another form of pigment giving the iron reactions occurs in 
certain pathological states. McCarthy has reported its occurrence in 
the brain of a rabbit killed by snake-venom. 

The changes of the nuclei first appear in the nucleolus; this, as has 
been said, normally contains one or two vacuoles. In degenerative 
processes it begins to swell, and more vacuoles develop, so that finally 
it presents the appearance that has been likened to the morula stage of 
the ovum. Ultimately, as the degeneration progresses, it may grow 
fainter and disappear entirely. Clumps of chromatin are often observed 
at the periphery of the nucleolus, and occasionally ray-like fibers pro- 
ject from them into the nucleus; accessory nuclei are also often present. 
Two or more nucleoli have also been observed, but it is doubtful if this 
is a morbid change, although Berkeley contends that it is an invariable 
sign of irritation. 

The nucleus itself exhibits a variety of changes. Stained with 
hematoxylin, it shows a delicate chromatin reticulum, and this may 
exhibit, in the ordinary forms of degeneration, changes that are found 
in other cells in the process of karyolysis; occasionally the chromatin 
collects in a diffuse, irregular mass about the nucleolus. In various 
forms of degeneration the nucleus seems to be stimulated, and shows 
karyokinetic figures, or may even divide completely, so that two nuclei 
are found in the same cell. This, however, is not necessarily a degen- 
erative change, because similar appearances are found in embryonal 
and in lacerated nerve tissue. Perhaps the most important nuclear 
change, and one that is most certainly pathological in nature, is the dis- 
location of the nucleus. It may be found at the periphery of the cell, or 
even protruding from it, as if to be expelled. It has been said that the 
nucleus can disappear from the cell when it does not present marked 
degenerative changes; it must be remembered, however, that the large 
diameter of the multipolar cell renders it possible with a good micro- 
tome to make a number of sections through a single cell, and it is very 
likely that these conditions are due simply to sections beyond the plane 
of the nucleus. In the most advanced types of degeneration the nucleus 
certainly disappears completely. 



896 



A TEXT-BOOK OF PATHOLOGY 



Changes may also take place in the cell as a whole. In the process 
of degeneration its outline usually becomes irregular and angular. The 
cell appears to be smaller, and often the pericellular space is very 
obvious. In many cases, however, this is an artefact, produced by the 
hardening fluid, and although it may be also the result of some morbid 
process it is impossible to give it any value as such. In the early 
stages of degeneration the protoplasmic processes may be unimpaired. 
Varicosities, such as shown by the impregnation, are rarely ob- 
served by the Nissl method. One of us has, however, seen them in 
the nerve-cells of the cord of a guinea-pig killed by tetanus. Tortuosity 
of the protoplasmic processes is very common, particularly in chronic 
conditions, such as sclerosis. It is impossible to stain the terminal 
ends by the Nissl method, and the changes in the gemmules cannot 
therefore be recognized. Sometimes the processes become friable, 
break off, and disappear completely, leaving the cells with a rounded 
outline. Finally, dislocation in the arrangement of the pyramidal cells 
of the cortex has been observed, particularly in cases of sclerosis of the 
brain, and it is probable that it occurs in all parts of the nervous system, 
although when the normal arrangement is irregular it is impossible to 
estimate its extent. 

The functions of the different portions of the nerve-cell are but 
imperfectly known. The neuraxon conveys impulses from the cells to 
the periphery, or transfers them in some as yet inexplicable manner in 
a variety of directions along the collaterals. The cell-body has a dis- 
tinct trophic influence over the neuraxon, and when this is removed, 
either by destruction of the cell or by the division of the neuraxon, the 
peripheral portion of the latter rapidly degenerates. On the other 
hand, the experiments of Goldscheider, Flateau, and Nissl have shown 
that the neuraxon exerts at least a temporary influence over the nerve- 
cell, and when it is destroyed in any way pathological changes invariably 
occur. There are many theories concerning the function of the nucleus, 
but no more is really known about it in the nerve-cell than in any other 
cell. It is concerned in active division, but this is apparently an exceed- 
ingly rare occurrence in nerve-cells. The protoplasmic processes have been 
regarded as nutritive or as centripetal organs. Lenhossek has suggested 
that the long axis-cylinders that convey impulses to the cells of the spinal 
ganglia are only a modified protoplasmic process. If this is so, it would 
be sufficient proof that they have an active function. The fact that the 
axis-cylinders of other cells terminate in arborization about the den- 
dritic processes, the cells forming the next link in the chain, is also a 
proof that even the short dendrites receive impulses. The fact that a 
single particularly thick dendrite may almost always be observed passing 
to the nearest blood-vessel indicates that they possess also some nutri- 
tive function, and that their extensive arborization is partly for the 
purpose of exposing as great a surface as possible to the nutritive fluid 
in which the cell is bathed. Concerning the pathological physiology of 
the nerve-cells we have at present little information, although certain 
definite changes have been described in cells that have been exhausted 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



897 



by excessive stimulation. What changes occur in the cell preceding 
the production of energy have not yet been determined. 

The nerve=fibers are of two kinds, the medullated and -the non- 
medullated. Non-medullated nerve-fibers consist of the axis-cylinder 
alone. They are found in the olfactory nerve and in the sympathetic 
nervous system, and when they undergo degeneration exhibit' swelling 
and varicosities, and ultimately break down into a granular detritus. 
Non-medullated herve-fibers may also be provided with a sheath, the 
neurilemma; such fibers are found in some of the cerebrospinal nerves. 
Medullated nerve-fibers may consist only of the myelin substance and 
the axis-cylinder — that is, the neurilemma is absent; such fibers are 
found in the central nervous system. Ordinarily, they consist of the 
neurilemma, the myelin substance, and the axis-cylinder; such fibers 
are found in the central nervous system and in the peripheral nerves. 
These fibers may branch, either giving off collaterals in their course or 
forming more or less complex aborizations at their terminations. The 
axis-cylinder usually exhibits a somewhat fibrillar structure. The 
myelin material resembles fat and has a high refractive index. It does 
not extend the whole length of the fibers, but at rather regular inter- 
vals is absent (nodes of Ranvier). These points are perhaps for the 
purpose of providing access for nutriment to the nerve-fiber. Upon 
the inner surface of the neurilemma are found a few oval nuclei sur- 
rounded by protoplasm. 

The function of the nerve-fibers is comparatively simple. Impulses 
are conveyed by the axis-cylinder, the neurilemma and the myelin 
substances apparently serving for protection and perhaps nutriment. 
It was formerly supposed that the myelin acted as an insulating mate- 
rial; but the fact that non-medullated fibers exist shows that in some 
cases at least it is unnecessary for this purpose. 

The earliest symptom of degeneration in the nerve-fibers is the 
appearance of granules in the myelin-sheath. These soon run together 
and form droplets that give all the reactions typical of fat. Such a 
fiber, examined microscopically in longitudinal section, exhibits these 
droplets arranged irregularly along its course, giving rise to a somewhat 
beaded appearance. The next change is usually found in the axis- 
cylinder. This may swell and become extraordinarily varicose, so 
that indeed it loses all resemblance to a nerve-fiber. Instead of being 
fibrillar, it has an irregular granular appearance, and may contain here 
and there minute droplets of fat, or the fiber may shrink and become 
granular, and ultimately disappear, nothing remaining to indicate its 
previous existence excepting a mass of delicate granular detritus. 
These changes may be brought about either by the destruction of the 
ganglion-cell from which the axis-cylinder forming the fiber arises, or 
by separation of the fiber from its ganglion-cell, or by injurious agencies 
acting locally upon the nerve-fiber. The second form of degeneration — 
that is, taking place in the peripheral portion of the cut nerve — is known 
as WaUerian. Changes in the proximal end also occur, but rarely 
extend further than the first node of Ranvier. When a nerve has been 



57 



898 



A TEXT-BOOK OF PATHOLOGY 



divided the earliest change is found on either side of the point of divi- 
sion, and consists in fragmentation of the myelin. About the third 
day fat-droplets appear in the myelin ; there is some swelling of the axis- 
cylinder, and often proliferation of the nuclei in the neurilemma may be 
observed. As the myelin breaks down into a fatty detritus, it is gradu- 
ally absorbed by the compound granular cells, which appear all along 
the course of the nerve-fiber, and at the end of three or four months 
it has entirely disappeared. During this period the neuroglia is under- 
going proliferation; at first there is a slight increase in the number of 
neuroglia cells; later, the proliferation of the fibers preponderates, and, 
finally, the degenerated area is occupied by a thick mass of coarse 
fibers that usually undergo slight contraction. The proliferation of 
the cells ceases about the time that the fibers have become completely 
degenerated. The subsequent proliferation, if any, occurs only in the 
neuroglia fibers. The central portion of the separated fiber will, after 
a long interval, also degenerate; this is possibly due to functional 
inactivity, and appears to be more of the nature of an atrophy. Thus 
in amputations that have occurred in early life, the anterior roots, 
forming the nerves that supply the amputated limb, become smaller 
and contain fewer fibers, and there is ultimately some degeneration in 
their ganglion-cells of the anterior horns. Regeneration of nervous 
tissue occurs in the invertebrates and possibly among fishes and reptiles, 
although this is very uncertain. Regeneration of nerve-fibers in the 
peripheral nervous system occurs in all the higher animals, including 
man. After the nerve-trunk has been cut, the peripheral ends of the 
axis-cylinder of the central portion of the nerve become swollen and 
split up into very fine fibrillse. These grow in various directions, and, 
if they unite with the distal portion of the nerve, will serve it as a skele- 
ton, and one of them, at least, will grow toward the periphery, ultimately 
forming new nerve-fibers. These changes occur in both sensory and 
motor fibers. (See section upon the Regeneration of the Peripheral 
Nerves.) 

Nerve-cell and fiber degenerations may be produced by endogenous 
toxins, such as those of uremia, or by the poisons of bacteria and proto- 
zoal diseases, and from exogenous poisons, such as lead and alcohol. 
It is probable that the changes vary with the cause in the early stages, 
but they are so seldom seen that it is difficult to be certain. The 
changes seem to take the form of chromatolysis and fatty degeneration 
in nerve-cells and granular or fatty change in the axis-cylinder and 
myelin-sheath. 

Disturbance of nutrition, either acting locally upon a terminal part 
of a nerve or by affecting the central cell, will cause degeneration, 
usually tending to travel toward the controlling ganglion-cell. Fatigue 
may cause degeneration of a nerve, but it seems that this is due to some 
primary change in the ganglion-cell. 

The neuroglia of the nervous system may proliferate or undergo 
softening, the former change producing various forms of sclerosis or 
gliosis. Sclerosis of the brain may be either diffuse or circumscribed, 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



899 



and the latter is again subdivided into the hypertrophic and atrophic 
forms. 

Diffuse sclerosis of the brain never involves all parts equally. To a 
certain extent it is normal in old age, and is usually found to be limited 
to the most superficial portion of the cortex beneath the pia, or else to 
the layer of the gray substance adjacent to the white matter. The 
neuroglia tissue in either situation appears to be composed of rather 
coarser fibers than normally, forming either wavy bands or a coarse 
network. Macroscopieally the brains exhibit only slight alteration. 
The consistency may, on account of other senile changes, be even 
slightly reduced ; the gray matter is usually narrower than normal ; the 
pia mater is generally firmly adherent, but not invariably. This con- 
dition sometimes occurs in connection with other diseases, as epilepsy, 
or may be congenital. 

Disseminated sclerosis is sometimes only slight in extent. It may 
occur in the brains of epileptics, of criminals, of old persons, and of 
idiots. Small sclerotic foci are usually found at the junction of the 
gray and white matter, more often in the former than in the latter. 
The neuroglia tissue forms a coarse, irregular network; as a rule, it is 
unusually vascular and without any or only a few true nervous ele- 
ments. These areas may be detected by the naked eye, when large 
enough, by the fact that they are paler than the surrounding tissue and 
often slightly sunken. If the process is more extensive and involves 
the whole thickness of one or more gyri, it gives rise either to an atrophic 
or hypertrophic form, or both may coexist in the same brain. The 
external appearance in these cases is characteristic and cannot be 
mistaken for any other process. 

In the atrophic form the gyri are reduced perhaps to the thickness 
of a lead-pencil, they are pale, firm, slightly granular upon the surface 
and the pia mater may occasionally be slightly adherent. Section 
through one of these convolutions shows that the cortex is considerably 
thinner and has a tendency to retract. The white substance is also 
involved, but apparently less severely. The extent of the process is 
very variable, one or two convolutions only being affected, or perhaps, 
as in several reported cases of epilepsy, only the cornua ammonis. 
Sometimes a number of convolutions are affected, and in the majority 
of these cases there is some tendency to an irregularly symmetrical 
distribution. Microscopically these lesions show marked hyperplasia 
of the neuroglia tissue — that is, increased number of neuroglia cells 
and coarseness of the neuroglia fibers, which form coarser meshes than 
normal. Many of the neuroglia cells are swollen, the nuclei are enlarged, 
pale, and the outlines of the cells are irregular. The nervous elements 
may appear to be more thickly placed and somewhat irregularly dis- 
tributed, and the protoplasmic processes of the ganglion-cells are often 
tortuous. More frequently they are considerably diminished in number 
or else entirely absent. The myelinated fibers are always decreased, 
particularly the tangential fibers of the cortex. The vessels are more 
numerous than usual and often show wide perivascular spaces filled with 



900 



A TEXT-BOOK OF PATHOLOGY 



fibrous tissue. In the most advanced areas, however, the vessels may 
be entirely absent. Corpora amylacea or other products of nerve 
degeneration are sometimes found. These changes are found in epi- 
lepsy and idiocy, and when the lesions occur in the motor region are 
always associated with motor disturbances. 

In the hypertrophic nodular form, the brain, as a whole, is usually 
somewhat enlarged, and nodules are found in the cerebral cortex that 
project from the surface and are much harder than the surrounding 
substance. The larger ones are often slightly umbilicated. The 
surface of these nodules is often granular. The microscopical changes 
are similar to those found in atrophic sclerosis, with the exception that 
the excess of neuroglia tissue is much more pronounced. In these 
brains there are often sclerotic areas beneath the ependyma of the 
ventricles, the lateral ventricles being more frequently affected than 
the third or fourth. These nodules are small, round, and very hard. 
Microscopically, they are found to consist of neuroglia fibers arranged 
in a somewhat concentric manner. They may be vascular or entirely 
deprived of blood-vessels, and sometimes contain chalky deposits or 
masses of hyaloid material. As in all destructive lesions of the central 
nervous system, secondary degenerations may occur, but they are far 
less common than would be suspected from the apparent extent of the 
degenerative processes. These forms of congenital sclerosis probably 
commence after the seventh month of fetal life, because, as Kundrat has 
pointed out, the arrangement of the convolutions is rarely disturbed. 
They have been ascribed to syphilis, to inflammatory change, to conges- 
tion of the lymphatic system, and to something akin to tumor formation. 
The absence of round-cell infiltration, and the fact that the pia is rarely 
adherent, even when the sclerosis takes place in the most superficial 
layers of the cortex, would seem to exclude inflammatory causation. 
Neurogliar proliferation occurs about gumma, but there is no ground 
for believing that all other forms are also due to syphilis. The dilata- 
tion of the perivascular spaces is favorable to the theory of congestion 
of the lymphatic system. This, however, is probably secondary. It is 
no explanation for this process to say it belongs to the tumors, but at 
present it appears impossible to give a more satisfactory etiology. 
Softening of the neuroglia is a part of all processes of softening in the 
brain, which are described in connection with thrombosis and embolism. 

THE BLOOD-VESSELS 

The arteries of the brain may be divided into two groups, those 
nourishing the cortex and those nourishing the basal ganglia. The 
former are the ramifications of the terminal branches of the circle of 
Willis; the latter arise directly from the main vessels of the base of the 
brain. 

Arteriosclerosis. — The changes that occur in the arteries are those 
ordinarily occurring in the vessels of the other parts of the body, 
atheroma of the arteries of the base of the brain being perhaps more 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



901 



frequent than of the arteries of other organs. These atheromatous 
changes usually lead to calcareous infiltration, and in old age often 
the entire circle of Willis is composed of typical pipe-stem arteries. 
When the process is less extensive, the calcareous infiltration is most 
apt to affect the two internal carotids, the middle cerebrals, and the 
basilar artery. 

Hyaline degeneration may also occur. It is of two kinds: that 
which forms simply the early stage of arterial sclerosis, and another 
process that is apparently independent of this and occurs as a diffuse 
degeneration of the intima and media. This latter form is frequently 
found in the brains of idiots even during early life. Occasionally 
it is also found in senile brains, but in these cases is not so certainly 
independent of arterial sclerosis. Amyloid change of the blood-vessels 
may occur as a part of general amyloid disease, but is not especially 
common in the brain. 

Colloid Degeneration. — A rare form of degeneration has been 
spoken of as colloid, although the material discovered in the blood- 
vessels seems more akin to that of hyaline degeneration. In this 
process the adventitia and the media are greatly thickened as a result 
of their infiltration with a homogeneous translucent material, which 
may be deposited irregularly in masses or. else cause a diffuse thicken- 
ing of the wall. The masses project into the surrounding nervous tissue, 
and may sometimes be detached, forming then independent clumps 
that are not unlike the so-called amylaceous bodies, although they fail 
to give all the characteristic amyloid reactions. This condition is 
usually associated with profound disturbances of the intellect, and may 
be associated with clinical symptoms that resemble those of general 
paresis. 

Syphilis frequently causes thickening of the intima or endarteritis , 
which may be due either to the usual round-cell infiltration or to the 
formation of fibrous tissue. Tuberculosis may also cause endarteritis. 
This form is most frequently associated with tuberculous meningitis, 
and therefore the basilar artery is the one commonly affected. 

Aneurysms may occur in any of the components of the circle of 
Willis. The basilar artery is the one most frequently involved, usually 
just at its posterior extremity. Large aneurysms of the arteries of the 
brain proper, or of the arteries of the vertex, are exceedingly rare. 
A saccular aneurysm, as large as a cherry, springing from the anterior 
communicating artery, was observed at the Philadelphia Hospital. 
Miliary aneurysms of the brain are, on account of their relation to 
cerebral hemorrhage, the most important form of vascular disease in 
the brain (see Fig. 215). These aneurysms may be ectatic or saccular. 
The ectatic forms are usually fusiform in shape, and often consist of 
but a single coat of the vessel wall; that is to say, they are merely endo- 
thelium surrounded by a thin layer of fibrous tissue. The saccular 
aneurysms are usually somewhat larger; they appear as bulbous swell- 
ings on one side of the vessel, connecting with the lumen by narrow 
openings. They may consist of a single wall, as in the fusiform type, 



902 



A TEXT-BOOK OF PATHOLOGY 



the most common variety, or of the intima or adventitia, with a con- 
siderable amount of fibrous thickening. Occasionally the fusiform 
aneurysms may exhibit distinct atheromatous change, but even in these 
instances the media is atrophic, and they are certainly exceptional. 
It is doubtful whether arteriosclerosis is of much importance in con- 
nection with the formation of these aneurysms, and it is certain that in 
the majority of cases the first change in the vessel is a fatty degeneration 
of the media. This leads to local weakening of the wall and to conse- 
quent distention — a change that is favored by the considerable degree 
of pressure to which the arteries springing from the middle cerebral 
or from the beginning of the basilar artery are subjected. According 
to some authors, these aneurysms are to be regarded as hernia? of the 
intima, really the result of atrophy of the muscularis; nevertheless, 
they are more frequent in the old, and certainly in the majority of cases 
in which they are found the arteries of the base are distinctly athero- 
matous. The formation of thrombi in miliary aneurysms is exceptional. 

CIRCULATORY DISTURBANCES 

Circulatory disturbances in the brain differ from those in other parts 
of the body on account of the presence of a rigid bony capsule (the 
skull), which prevents any increase or decrease in the size of the con- 
tained viscus. Variations in the quantity of blood, however, do take 
place in adults, and are rendered possible, first, by the elasticity of the 
nervous substance itself, which is capable of undergoing a slight degree 
of compression or extension, and, second, by the free communication 
of the subarachnoid spaces of the brain and cord and the ventricular 
cavities, so that the cerebrospinal fluid may be in greater or less quantity 
in the cavity of the skull or in the spinal canal, and thus permit varia- 
tion in the amount of blood in either region. Local congestion or anemia 
may occur as a result of local disturbances, but the free anastomosis 
of the arteries of the circle of Willis provides such facility in equalizing 
the amount of blood flowing to the different parts of the brain that 
neither is often found in general conditions. In very young children 
these mechanical restrictions do not obtain, because the fibrous union 
between the bones of the skull permits of very considerable changes in 
the size of the cranial cavity. 

Acute anemia of the brain may occur as a result of severe hemor- 
rhage, or of hyperemia in other parts of the body, particularly the 
pulmonary and abdominal organs, and it has been supposed to exist 
in fainting, during hysterical crises, and in sleep. It must be admit- 
ted, however, that certain proof of its existence either as a cause or 
effect of these conditions is lacking. Microscopically, the brain is 
usually pale and firm. There is little or no tendency on the part of the 
small venules of the white substance to bleed upon cross-section, and the 
gray matter is distinctly paler, so that the distinction between it and the 
medullary substance is not so distinct as is the case in normal tissue. 
Sometimes in these conditions there is overfilling of the veins of the 
pia as a result of the shrinking of the brain. The changes in the func- 



DISEASES OF THE BRAIN AND ITS MEMBRANES 903 

Hons of the brain tissue ascribed to this condition are partly irritative, 
partly paralytic. They are very indefinite. 

Chronic anemia of the brain may occur in severe cachectic condi- 
tions, such as progressive pernicious anemia, lead- or malarial poison- 
ing. It may also be the result, though less frequently, of atheroma of 
the cerebral arteries, with a general narrowing of their lumina. The 
brain is small, the consistency varies according to the duration and 
nature of the process, being at first hard, later, probably as a result 
of degenerative changes, slightly softer than normal. The ventricles 
are not dilated at first, but the convolutions are shrunken and the sulci 
are wider as a result of the diminution in size of the brain as a whole. 
The substance of the brain is pale, and often seems slightly moister than 
normal. Local anemia may occur as a result of thrombosis or embolism, 
and usually leads to softening. 

Active hyperemia of the brain is nearly always associated with 
inflammatory or toxic conditions. It is perhaps most frequent in 
association with meningitis or encephalitis. It is always found after 
death from sunstroke, acute delirium, cholera, and hydrophobia, as 
well as, occasionally, after death from infectious disease. It may be 
local or general. 

Local hyperemia is usually associated with meningitis, and may be 
limited to the superficial layer of the cortex beneath the meningitic 
areas. The affected parts are darker than normal and may even contain 
punctiform hemorrhages. Microscopically the blood-vessels are found 
to be dilated, and there is more or less degeneration of the adjacent 
nerve substance, according to the duration of the process. Local hy- 
peremia may also occur after thrombosis, and leads to red softening 
of the nerve tissue. 

General Active Hyperemia. — The brain is darker and larger and its 
consistency is softer. The blood-vessels of the pia are injected. The 
gray matter is darker and, as in the local form, may contain minute 
hemorrhagic foci. The white matter is moist; its color is rarely altered, 
but as soon as the section is made it is covered with small red spots, 
representing hemorrhages from the veins and capillaries. These may 
be readily distinguished from interstitial hemorrhages by allowing a 
little water to flow over the surface of the section, when they will disap- 
pear. Microscopically, aside from the distention of the vessels with 
blood, pronounced degenerative changes are rarely found, excepting 
in those cases resulting from infectious diseases. In these the altera- 
tions commonly associated with severe toxemia are present, but are 
to be considered as complications and not as the result of the circula- 
tory disturbances. 

Occasionally, in acute infectious diseases such as typhoid fever, a 
condition occurs in which there is evidently excessive irritation of the 
central substance, manifested by symptoms not unlike those of menin- 
gitis. Postmortem in these cases the only changes found are hyper- 
emia of the brain. Even microscopically no distinct inflammatory le- 
sions can be discovered. This condition has been termed meningismus. 



904 



A TEXT-BOOK OF PATHOLOGY 



Passive hyperemia may be associated with valvular heart disease 
or chronic lung disease, or it may be caused by tumors in the neck 
pressing upon the jugular veins, or by intracranial conditions. Of the 
latter, the most important are brain tumors compressing the veins, 
whilst the arteries still continue to convey blood and thus cause increase 
of the cranial contents. When the tumors press upon the veins of Galen 
passive hyperemia and distention of the ventricles are particularly 
common. Passive hyperemia may also be caused by thrombosis of 
the dural sinuses. In acute passive congestion the veins of the dura 
are widely distended; the subarachnoid space is moist; the brain seems 
to be slightly larger, softer and moister than normal. The gray matter 
is of a slaty color. The white matter may have a faint bluish tinge, and 
its capillaries and ventricles bleed freely upon cross-section. The ven- 
tricles may not be larger, but appear to contain fluid under pressure 
that wells forth when they are opened. 

Edema of the brain nearly always occurs when passive hyperemia 
persists, and also occurs in cases of chronic alcoholism. It is 
characterized by the distention of the subarachnoid space with 
liquid, so that the convolutions are no longer distinct and the sur- 
face of the brain has a clear or pearly appearance. The arachnoid is 
usually thicker, particularly along the sulci. The fluid is clear, or 
perhaps very slightly turbid; it has a higher specific gravity than the 
cerebrospinal liquid, coagulates upon boiling, and is usually found to 
contain numerous cellular elements. A microscopical examination of 
the brain and its membranes shows marked distention of the sub- 
arachnoid space, which is usually divided into irregular spaces by deli- 
cate fibrous bands. The endothelial cells appear to have undergone 
some proliferation, and in many places have desquamated and lie free 
in the areolar spaces. Around the blood-vessels there is occasionally 
slight extravasation of round cells, which are usually mononuclear and 
resemble lymphocytes, and indicate an inflammatory reaction to the 
long-continued pressure. The arachnoid is usually thicker, the thick- 
ening being almost exclusively fibrous in nature. The pia is slightly 
thicker, and sometimes may be seen to have coalesced with the super- 
ficial layer of the cortex. In the brain substance the perivascular spaces 
are distended, the neurogliar meshwork is coarser than normal, and 
there may be slight evidences of degeneration in the cells. 

Local edema of the brain, the so-called apoplexia serosa, is occa- 
sionally found in the neighborhood of areas of softening. In cases of 
acute hydrocephalus this serous infiltration sometimes occurs in the 
neighboring internal capsules, and may even lead to transient hemi- 
plegia. 

Cerebral hemorrhage occurs in two varieties: the so-called punc- 
tate form and massive hemorrhage. 

Punctate hemorrhages are due to some alteration of the vessel walls 
or of the degree of blood-pressure, causing extravasation of blood into 
the surrounding tissues. The commonest causes are mania, convul- 
sions and encephalitis, and severe infections. The hemorrhages are 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



905 



small, often microscopical, and are by far most common in the gray 
matter, especially in the cortex. The principal causes are hyperemia, 
particularly if associated with inflammatory conditions of the brain, and 
convulsions. The wall of the blood-vessel may be diseased, but does 
not always show solution of continuity, or the hemorrhage may burrow 
along beside the vessel like a dissecting aneurysm, but yet free against 
the nerve tissue. The blood-pigment is more or less altered, according 
to the length of time that has elapsed between the occurrence of the 
hemorrhages and the examination of the tissues. The nervous tissue 
immediately involved is edematous, and there is usually some prolifera- 
tion of the neuroglia cells in the vicinity. Such hemorrhages, of course, 
may heal without leaving any trace, for the secondary degenerations 
that may possibly be caused are too slight to be detected. 

Massive hemorrhages usually occur from the branches of the middle 
cerebral artery — that is, from the vessels most frequently the seat of 
miliary aneurysms. The arteries commonly involved are the len- 
ticulostriate and lenticulothalamic branches of the middle cerebral 
vessel, and the hemorrhage occurs in the internal capsule. These 
vessels have no anastomoses. Hemorrhages may occur in the centrum 
ovale or the pons, or, in fact, in almost any portion of the central ner- 
vous system. The attack is precipitated by a sudden strain, of physical 
or mental nature, upon a diseased vessel or upon an aneurysm. The 
blood usually collects in the form of an irregular dark-red mass that in 
recent cases rapidly becomes bright red upon exposure to the air. 
The size of the hemorrhagic area naturally varies with its location and 
the amount of blood extravasated. Its outline is exceedingly irregular, 
and almost always separate small hemorrhagic foci are found in the 
surrounding tissue. According to the density of the tissue, the blood 
is more or less dispersed. Thus, in the white matter the extravasation 
is usually more diffuse than in the gray, where hematomata are exceed- 
ingly apt to form. The substance of the brain is soon softened. Its 
structure is usually entirely lost, although it may be possible in recent 
cases to recognize the presence of altered cells and nerve-fibers. The 
neuroglia usually shares in this softening, but if the hemorrhage is not 
extensive, it may remain and form a sort of skeleton for the blood-clot; 
the tissue then is not nearly so soft, and the surface upon section usu- 
ally is smooth. If the hemorrhage occurs in the internal capsule, as is 
usually the case, and is at all extensive, the blood may creep inward 
toward the ventricle, into which it may rupture, filling the lateral 
ventricle and sometimes extending into the third ventricle and into the 
lateral ventricle on the other side (Fig. 427). Occasionally, in exceed- 
ingly severe cases, almost the whole of one of the hemispheres may be 
destroyed; this is usually associated with sudden death, and is known as 
the foudroyant form of apoplexy. The softened brain substance can 
usually be readily washed away by a current of water, leaving the blood- 
vessels, which should then be examined with a low power for the pres- 
ence of miliary aneurysms. If the patient survives his first attack, 
rapid alterations begin to take place in the diseased tissue. The throm- 



906 



A TEXT-BOOK OF PATHOLOGY 



bus contracts, causing edema in the surrounding tissues. A capsule 
of delicate fibrous tissue may even be formed about it. The small 
hemorrhages in the surrounding tissue are absorbed. The color of 
the softened region becomes dark brown, and it may either go on to 
complete liquefaction, with the subsequent absorption of the pigment 
and the formation of a cyst, or else be gradually entirely absorbed, 
leaving a pigmented scar. The walls of the cysts are usually discolored 
by pigment, and in the neighborhood pigment-granules and compound 
granular cells are found in great numbers. These old hemorrhagic cysts 
are very difficult to distinguish from those produced by other forms of 
softening. Often the contents are slightly discolored, the walls are 
dense and somewhat sclerotic in nature, and may contain crystals of 
hematoidin. It is somewhat doubtful whether the walls are com- 
posed of neurogliar tissue or of true fibrous connective tissue derived 




Fig. 427. — Hemorrhage into the internal capsule and the caudate and lenticular nucleus 
of the right cerebral hemisphere (from Bollinger). 

from the blood-vessels. It is certain, however, that shortly after ex- 
travasation of the blood, hyperplasia of the neuroglia in the immediate 
vicinity takes place. This may occur very rapidly, so that in the course 
of a few days new neuroglia fibers may be seen pushing their way into 
the hemorrhagic area from the collection of neuroglia cells in the nearest 
healthy tissue. After healing has taken place the hemisphere is usually 
reduced in size. This reduction is not merely equivalent to the amount 
of nerve tissue that has been destroyed, but represents also the secondary 
degeneration that occurs in the nerve-fibers whose course has been 
interrupted by the lesion. This is both ascending and descending, and 
frequently causes sclerosis that involves not only the brain, but extends 
throughout the pyramidal columns. 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



907 



Pathological Physiology. — The disturbances in the functions of the 
central nervous system produced by hemorrhage are among the most 
interesting in the domain of nervous physiology. At the time of the 
rupture of the vessel the patient almost invariably becomes suddenly 
unconscious and falls, the face is flushed, and there may be convulsive 
movements. This is termed apoplexy. The period of unconscious- 
ness may persist for a longer or shorter interval, according to the amount 
of hemorrhage that has taken place. If the patient recover, the sub- 
sequent changes depend upon the situation of the hemorrhage and 
the extent of the destruction of nervous tissue that has taken place. 
As will readily be seen from the description of the pyramidal tract, 
lesion in any part of its course above the first cervical segment produces 
paralysis of the opposite side of the body; if above the middle of the 
pons, paralysis of the lower portion of the face on the opposite side is 
also produced; if below this point, paralysis of the same side. Mono- 
plegias are likely to occur if only a small portion of the fan-like projec- 
tion fibers of the pyramidal tract is involved, such as would be produced 
by a lesion in the cortex or in the centrum ovale. In all these cases only 
the superior motor neuron is affected, and in consequence, either because 
some inhibitory influence is removed or because the lower motor neurons 
are irritated by the products of degeneration, a condition of spasticity 
arises in the muscles. Subsequently, their nutrition is impaired and 
they contract. An interesting series of disturbances is produced by 
lesions occurring in those portions of the cortex that have to do with 
manifestations of speech, either receptive or motor. If the former are 
involved, we speak of it as amnesia; if the latter, as aphasia. Lesions 
of the optic tract posterior to the chiasm cause hemianopsia. 

Secondary Degeneration after Hemorrhages. — As a result of hemor- 
rhage into the brain substance with destruction of tissue secondary de- 
generations appear, which, of course, are systemic and follow the direc- 
tion in which the nerve-fibers convey impulses. Of these the most 
important are the degenerations of the pyramidal tract, of the optic 
tract, and of the projection fibers from the temporosphenoid lobes. 
A discussion of this subject involves consideration of the anatomy of 
the brain more than of the pathology, and only the most important 
details can be given here. Degeneration of the pyramidal tract may be 
sharply circumscribed if the focal lesion is situated in the cortex or the 
centrum ovale. In this case a slender band of degenerated fibers may 
be traced along the pyramidal tract. This is only possible, however, 
if the lesion is sufficiently recent to permit the employment of Marchi's 
staining method, for otherwise it is impossible to recognize a small 
number of degenerated fibers in the midst of a group of healthy ones. 
As the hemorrhage usually takes place from the lenticulo-caudate 
artery and involves the complete destruction of the pyramidal fibers 
in the internal capsule, it not infrequently happens that the entire 
pyramidal column of one side undergoes secondary degeneration. 
Interruption of the fibers of the optic radiation, or destruction of the 
primary optic centers, causes secondary degeneration which does not, 



908 



A TEXT-BOOK OF PATHOLOGY 



however, appear as promptly as in the motor fibers. There is degener- 
ation in the external geniculate body, in the pulvinar, and in the anterior 
corpus quadrigeminus of the same side. Ultimately, degeneration may 
also occur- in the optic nerves. Destruction of the second and third 
temporal lobes, or of the projection fibers arising from them, causes 
secondary degeneration in the posterior limb of the internal capsule. 
The fibers appear to extend into the thalamus, and also into the crusta. 
Destruction of other parts of the brain cortex causes degeneration, 
which seems to affect chiefly the projection fibers. Extensive hemor- 
rhages into the cerebellum usually cause death, as a result of pressure 
upon the medulla. If, however, the patient survive, and if the nucleus 
dentatus be particularly involved, there is degeneration of the superior 
cerebellar peduncle, which may be traced as far as the red nucleus in 
the tegmentum. All these secondary degenerations are quite typical 
in character. They appear about the ninth day, the first changes being 
the degeneration of the myelin-sheath. This is followed by the appear- 
ance of compound granular cells and hyperplasia of the neuroglia, and 
later corpora amylacea may sometimes be found. Ultimately nothing 
but the neuroglia remains, and this is composed of coarser fibers than are 
found in normal nervous tissue. Occasionally, nerve-fibers without 
myelin-sheaths are found traversing the sclerotic tissue. 

Thrombosis and embolism of the vessels of the brain are due 
to causes that produce the same processes in other parts of the body. 
Embolism will produce attacks of apoplexy like massive hemorrhage; 
but thrombosis, while causing paralysis and nerve-tract degeneration, 
does so much more slowly. Thrombosis may occur anywhere. It is 
perhaps more frequent in the basilar artery than in other situations, 
but this rule is by no means certainly established. The causes are, 
of course, chiefly atheroma of the vessels or syphilitic endarteritis. 
Embolism, on the other hand, usually occurs in the artery of the Syl- 
vian fissure. Perhaps 80 per cent, of all cases occur in this situation. 
This frequency is due to the fact that the course of the blood is direct 
from the heart to this vessel, and its importance lies in the fact that it 
is an end artery and, therefore, its occlusion is most apt to lead to cerebral 
necrosis. Less frequently an embolus will lodge in the anterior cerebral, 
but it is probably extremely rare for an embolus to travel along the 
posterior communicating artery and lodge in the posterior cerebral. 
A more frequent route of embolism into the latter artery is along the 
vertebrals to the basilar. Embolism in the basilar artery can, of 
course, never occur, as its lumen is greater than that of either of the 
branches from which it receives blood. A saddle embolus may occa- 
sionally lodge at its bifurcation and give rise to local thrombosis. 
Sometimes the two processes occur simultaneously — that is, fragments 
of a parietal thrombus in one of the vessels may be washed off into the 
blood-stream and be carried along the artery until they occlude its 
lumen or that of one of its branches. The results of embolism or throm- 
bosis may be either infarction, or, if the obstruction takes place slowly, 
as in thrombosis, it then being possible for a collateral circulation to be 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



909 



established, there may be no changes or only temporary results. The 
functional disturbances are very similar to those of hemorrhage. As, 
however, the lesions frequently occur very slowly, the sudden shock 
may not occur and the paralysis may supervene without any period of 
unconsciousness. 

Infarction of the brain usually leads very rapidly to cerebral soften- 
ing (encephalomalacia) . It has been usual to describe three forms — red, 
yellow, and white — which, while frequently pure in form, are at times 
but stages of the same process, and they do not constitute separate 
pathological entities. 

Red softening corresponds very closely to the hemorrhagic infarct. 
It consists of a serous infiltration of the tissue, the extravasated liquid 
containing numerous red corpuscles. The same theories that have 
been suggested for the explanation of a hemorrhagic infarct have been 
used to explain its occurrence. 

Yellow softening is really only the red softening after more complete 
liquefaction has taken place and most of the pigment has been absorbed. 

White softening is a term applied to two very different conditions. 
The first corresponds to the anemic infarct, and appears very shortly 
after the occlusions of the vessels. The second is a late stage of any 
form of softening, and is characterized by the occurrence of an excessive 
amount of fat in the softened area, producing an emulsion. The white 
color becomes even more pronounced after the fat has been absorbed, 
and the lesion is represented only by coarse neuroglia fibers. Micro- 
scopically, the earliest changes usually appear toward the end of the 
first twenty-four hours. The brain substance in the softened area is 
swollen, softer, and somewhat mottled in appearance and may even 
exhibit small punctiform hemorrhages. The lesion is not sharply 
delimited, but fades gradually into the surrounding tissues. 

If a large artery has been obstructed, a considerable portion of the 
brain may be softened and there will be a large extravasation of blood. 
In this case the parts of the brain showing the greatest alteration are 
those nearest the periphery of the distribution of the obstructed vessel, 
and these changes may even occur without complete obstruction if the 
general circulation is impaired, as in valvular heart disease, or as a 
result of profound general anemia. As the process continues, more and 
more blood is extravasated into the tissue, giving it a bright-red appear- 
ance. The lesion by this time becomes more circumscribed, although the 
surrounding tissue may be somewhat softened, and, as in the case of cer- 
ebral hemorrhage, may contain punctiform hemorrhages. As soon as the 
demarcation is complete the brain tissue becomes rapidly softer, prob- 
ably as a result of the obstruction of the lymph-channels by which the 
nutritive fluids enter. The nerve-cells undergo almost complete degen- 
eration; they lose their axis-cylinders and their tinctability, and may 
either disappear completely or be no longer recognizable. The myelin- 
sheaths undergo a fatty degeneration, in which the nerve-fibers soon 
take part. The whole tissue is filled with compound granular cells. 
The neuroglia fibers may also become softened and, to a large extent, 



910 



A TEXT-BOOK OF PATHOLOGY 



liquefied, although they persist longer than the other elements. The 
wall of what has now become a cyst is composed of the surrounding 
neurogliar tissue, newly formed capillaries, and nervous tissue in an 
advanced stage of degeneration. The blood-vessels, however, usually 
persist for some time, although they are filled with thrombi and form 
an irregular spongy network in the lesion. 

When organization commences the blood-pigment gradually disap- 
pears, and the material changes from a brownish, turbid fluid to a lighter 
yellow mass, often irregularly surrounded by deeply pigmented cells. 
Later, complete contraction takes place, and a scar, composed chiefly 
of neuroglia tissue, but also containing some fibrous connective tissue 
that has developed from the walls of the blood-vessels, is left. It is, 
of course, clear that red softening is more frequent in the vascular parts 
of the brain, and white softening in those regions that are poorly sup- 
plied with blood, particularly in the white substance of the cerebrum. 
The areas are rarely as well circumscribed as those of red softening, and 
often do not lead to complete destruction of the tissue, causing only 
numerous adjacent minute focal lesions, the so-called etat crible. 

A peculiar form of softening occurs in the cortex of the brain. It is 
usually found in lesions that have existed for some time. The area is 
yellow, depressed, and somewhat circumscribed. The pia mater over 
and around the lesion is somewhat thickened, and often the surround- 
ing blood-vessels show thickening of the walls, although this latter 
change is probably the cause and not the result of the gross lesion. 
These are the so-called plaques jaunes of French writers, and if extensive 
they lead to considerable retraction of the brain substance and to the 
formation of collections of liquid in the subarachnoid space {hydrops e 
vacuo; external hydrocephalus). 

Areas of softening, probably due to capillary thrombosis, are fre- 
quently found in children suffering from tuberculous meningitis. They 
may also occur in other forms of meningitis, and also in encephalitis, 
although in these latter conditions the presence of pyogenic micro- 
organisms in the emboli lead to somewhat different changes, which 
will be described in connection with encephalitis. Traumatism may also 
cause softening, often multiple in character, and not necessarily situated 
directly beneath the point of injury. As a result of the destruction of 
tissue, secondary degenerations occur that differ in no respect from 
those following hemorrhage. 

INFLAMMATION 

Encephalitis, or inflammation of the brain substance, is prob- 
ably not essentially different from inflammation of the other tissues in 
the body. The nature of nervous tissue, however, and the peculiar 
reaction that it manifests to various injurious agencies, render this 
subject one of the most doubtful and difficult in the pathology of the 
central nervous system. The various forms may be classified, first, as 
acute and chronic. The important forms of acute encephalitis are the 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



911 



parenchymatous, the simple, the hemorrhagic, and the suppurative. 
Chronic encephalitis may take the form either of sclerosis or of scar- 
formation, the latter really only a modification of the former. Acute 
encephalitis may be considered to be disseminated or focal. No case 
has been recorded in which there was generalized inflammatory change 
in the brain, and it is inconceivable that such a condition should be 
compatible with life. 

Acute parenchymatous encephalitis is rather a form of degeneration 
than of specific inflammation. Changes in the nerve-cells without 
associated vascular phenomena have been observed and described in 
a number of intoxications, either the result of direct poisoning or in- 
fection. More or less extensive changes have been recorded as a 
result of poisoning by alcohol, arsenic, and other poisonous substances. 
Of the infectious diseases that have been studied, the most important 
are diphtheria, tetanus, leprosy, and hydrophobia. The changes differ 
somewhat in nature, and, of course, in the different cases, considerably 
in degree. The most important and typical have been already described 
in the section upon degeneration of the nerve-cells. These forms of 
encephalitis, if the name may properly be applied to them, may lead 
to death, but recovery even from the advanced stages is not impossible. 
Neither the brain nor the cord in these cases exhibits any macroscopical 
changes, excepting, perhaps, passive congestion of the membranes 
when death was preceded by violent convulsions, as in tetanus. 

Simple acute focal encephalitis is characterized by the development, 
in various parts of the brain, of areas of softening that may range from 
a millimeter to several centimeters in diameter. They are usually 
irregular in size and very indistinctly separated from the surrounding 
tissue. The most common situations are the region of the third and 
fourth ventricles and the aqueduct of Sylvius. The gray matter is 
more often involved than the white. Polioencephalitis is a localized 
cerebritis of the basal ganglia bulb or pons, or all of these, affecting 
chiefly the motor ganglia, with cytolysis, and some cellular infiltration 
around them and about the blood-vessels. It is more extensively con- 
sidered under Poliomyelitis. 

Etiology. — The cause is probably in all cases the presence of infec- 
tion in the body, such as influenza, typhoid fever, or septicemia. 
Authors, whose opinions we must respect, have, however, described 
encephalitis as the result of simple concussion of the brain, or of various 
forms of poisoning, such as lead. The difficulty in the latter group of 
cases is due to the close resemblance between encephalomalacia and 
encephalitis. Collections of round cells, with slight degenerative changes 
in the nervous system, have been described in chorea, and have been 
supposed to represent the subacute or chronic form of encephalitis. 
The observations are, however, at present insufficient to establish this 
point. References will be made again to it under the heading of Chronic 
Encephalitis. 

Pathological Anatomy. — The two most important changes are 
those in the color and consistency. The former is usually slightly 



912 



A TEXT-BOOK OF PATHOLOGY 



darker than normal, but may, if, as is not unfrequently the case, exten- 
sive hemorrhage has occurred, become a bright red, resembling, upon 
inspection, an area of hemorrhage, or perhaps more closely, an area of 
red softening. The consistency is always decreased, probably as a 
result of serous infiltration. Often the diseased area projects slightly 
from the surface of the section. Microscopically, the characteristic 
change is the perivascular round-cell infiltration. This usually involves 
the majority of vessels in the lesion, and may also be found in regions 
of the brain in which softening has not already commenced. Usually 
there is the characteristic inflammatory congestion, the blood-vessels, 
particularly the small capillaries, being sometimes greatly distended 
and packed with red blood-cells. In some cases thrombi have formed. 
Hemorrhages are exceedingly frequent; these are sometimes punctiform 
and sometimes diffuse extravasations into the tissue. Often they appear 
to represent ruptured capillaries, and produce a peculiar speckled appear- 
ance on the surface of section. In the early stages the cellular exudate 
is chiefly composed of polynuclear leukocytes. If the process is more 
advanced, these may exhibit more or less degenerative changes. Later 
they are replaced by mononuclear cells, probably representing prolifera- 
tion of the endothelial cells, and perhaps of the neuroglia cells. The 
ganglion-cells in the inflammatory region undergo rapid degeneration, 
usually passing through various stages of chromatolysis, until they are 
reduced to little colorless vesicles of irregular form. The nerve-fibers 
also degenerate; the myelin forms fatty droplets; the axis-cylinders at 
first swell and then share in the granular disintegration. In the midst 
of the focus the neuroglia ordinarily shares in the softening. At the 
periphery there is usually a noticeable proliferation of the neuroglia 
cells and the formation of a coarse, thick network of neuroglia fibers. 
Of course, these changes are not found about very early lesions. In 
the earliest stages compound granule cells are usually absent ; later they 
may appear in considerable numbers, but their presence is by no means 
sufficient to indicate the existence of an acute or chronic inflammatory 
process. Disappearance of the tangential fibers in the cortex, in lesions 
situated in this area, have also been described. Ordinarily, in these 
forms of encephalitis, the rest of the brain exhibits no macroscopical 
changes, and often none can be detected by the microscope. The 
membranes are smooth, the vessels of normal elasticity, and not sur- 
rounded by a round-cell infiltration. Complete resolution may perhaps 
occur; of course, this can only be supposed from the clinical symptoms 
of the disease, there being no definite experimental or pathological evi- 
dence to support it. 

The focal lesions may undergo softening and lead ultimately to scar- 
formation, and if they are extensive there will be considerable atrophy 
of the affected part of the brain. The great majority of cases, however, 
in all probability terminate fatally. The nature of the process is gener- 
ally accepted to be primarily vascular, the secondary changes being the 
result of alteration in the nutrition of the surrounding part. 

Suppurative encephalitis has already been in part described in con- 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



913 



nection with purulent meningitis. In that condition, the pyogenic 
emboli appear to enter the brain substance along the lymphatics that 
dip into it from the pia. They are usually small, not circumscribed, 
and more apt to be found in the gray matter of the cortex, particularly 
near the base of the brain and in the structures adjacent to the ventricles, 
than in the white substance. Occasionally larger collections, forming 
rather ill-defined abscesses, are found. In a brain that one of us removed 
at autopsy the changes in the pia arachnoid were slight and were limited 
to a small area over the motor region for the leg on the left side, but 
beneath this there was an extensive area of purulent infiltration of the 
brain substance, not sharply circumscribed. 

Abscess of the brain is a condition characterized by the presence 
in the brain substance of one or more cavities containing pus. The 
usual cause is suppurative bone disease, particularly that resulting 
from otitis media. This condition may, however, occur in general 
pyemia as a result of metastasis from some neighboring or remote focus 
of suppuration. Suppuration may also occur in the course of pneu- 
monia, or in chronic suppurative diseases of the lungs, such as fetid 
bronchitis. Direct infection of the brain, either experimentally or as 
a result of wounds penetrating the skull, has also been observed. In 
many of these cases the nature of the transmission is clear; thus the 
abscess resulting from otitis media, disease of the ethmoidal sinuses, or 
from direct inoculation, is usually situated in the immediate neighbor- 
hood of the original focus. Abscess secondary to pulmonary disease 
is usually found at the base of the cerebral hemispheres, and is probably 
transmitted along the retropharyngeal lymphatics. Abscess due to 
injury without penetration of the skull has occasionally been recorded ; 
sometimes it is found in the contused area, sometimes on the opposite 
side of the brain. The micro-organisms that have been found in the 
pus include practically all the pyogenic forms. The most frequent are, 
perhaps, the staphylococcus, the streptococcus, and the pneumococcus. 
Occasionally the actinomyces, the Bacillus pyocyaneus, and the Myco- 
bacterium tuberculosis have been found, the latter in cases that were 
apparently acute abscesses of the brain, and not softened solitary 
tubercles. 

Statistical studies of the literature show that in about two-thirds 
of all cases the cerebrum is the seat of the lesion; in the remaining 
third it is chiefly the cerebellum. This distribution does not, of course, 
apply to the disseminated forms of purulent encephalitis. Solitary 
abscesses are usually the result of embolism or extension from the 
bones. They may be small or of considerable size, and one is on record 
from which 400 c.c. of pus were removed. They may be either sur- 
rounded by softened brain substance or distinctly encapsulated. The 
latter condition usually occurs if they have lasted any length of time — 
that is, three or four weeks ; although cases are on record in which a dis- 
tinct wall did not develop about an abscess that had existed for several 
months. The contents of the cavity are pus and detritus, and in it may 
frequently be found thrombosed blood-vessels. The surrounding brain 

58 



914 



A TEXT-BOOK OF PATHOLOGY 



tissue is usually undergoing softening. It may be either white, or, as a 
result of hemorrhagic extravasation, red in color. The abscesses usually 
spread more or less gradually ; that is to say, there is probably no tend- 
ency to heal spontaneously. If large, they cause considerable intra- 
cranial pressure, which is indicated by the flattening of the convolutions 
or bulging of the brain after the skull has been trephined. Those due 
to punctured wounds are usually associated with meningitis. Those 
due to caries must also be associated with inflammatory changes in the 
meninges, and not unfrequently there is thrombosis of the cerebral 
sinuses. Microscopically, we find the ordinary characteristics of pus. 
The wall or periphery is usually undergoing fatty degeneration, and 
there is a considerable accumulation of round cells in the surrounding 
tissue. Metastatic abscesses are usually multiple. A group may be 
found either in one situation in the brain or they may be very widely 
distributed. In cases of severe encephalitis more or less pronounced 
changes may be observed in the ganglion-cells in other parts of the 
central nervous system. 

Primary Acute Hemorrhagic Encephalitis. — Striimpell described 
under this name a form in which the dura was normal but somewhat 
dry; the pia injected, the centrum ovale softened, edematous, slightly 
pinkish or gray, and marked by fine hemorrhagic points. Microscopic- 
ally there were no granular cells, but drops of myelin and some detritus. 
There was some hyperemia and cellular infiltration of- the pia. The 
ganglion-cells of the cortex were normal. In the white matter the 
vessels were distended with blood and surrounded by thick masses of 
round cells; the perivascular spaces were distended; the neurogliar 
tissue coarser than normal. In many situations there was bleeding 
from the capillaries. 

Chronic encephalitis may take the form of sclerosis or of 
scar-formation, which is really but a variety of sclerosis. (See 
Neuroglia.) 

Lobar sclerosis is usually an extensive but sharply circumscribed 
process affecting the whole or part of one or more lobes of the brain. 
The involved area is usually considerably diminished in size. The 
convolutions are smaller, the sulci broader, but, of course, not so deep; 
the surface is often finely granular, and the pia is adherent. The con- 
sistency is greatly increased, the tissue being almost like cartilage. 
Microscopically there are the same changes found in the other forms — 
that is, excessive proliferation of the neuroglia, with partial or complete 
disappearance of the nervous elements. The cause appears to be some 
vascular disturbance occurring during fetal existence, as the localiza- 
tion nearly always corresponds to the distribution of one of the arteries 
supplying the brain. If the anterior cerebral artery is affected, the 
frontal lobe is sclerotic. If the artery of the Sylvian fissure is involved, 
there will be sclerosis of all the hemisphere, with the exception of a part 
of the occipital lobe; and if the lesion is situated on the proximal side 
of the lenticulostriate artery, this part will also be degenerated. If 
the posterior cerebral artery is occluded, the lesion will be found at the 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



915 



tip and in the lower half of the occipital lobe. Extensive secondary 
degeneration always occurs in this form. 

Multiple or disseminated sclerosis is a condition characterized by 
the formation throughout the nervous system of various foci of irregular 
size and distribution in which the neuroglia is somewhat hyperplastic, 
the myelin-sheaths more or less degenerated, and the axis-cylinders, as 
a rule, slightly, if at all, affected. When sclerotic areas affect the white 
matter of the brain and cord they appear as grayish or grayish-pink 
areas, which may, if at the surface, be observed through the pia. They 
resemble the gray matter of the cord too closely to be clearly distin- 
guished from it. Their edges are usually sharp. After hardening in 
Midler's fluid they appear of a bright yellow color and are exceedingly 
distinct. The smallest may be only a millimeter in diameter, and the 
largest may occupy the whole transverse section of the spinal cord or 
even entire convolutions of the brain. Occasionally sclerotic areas 
may be found in the nerve-roots. The most important change that is 
found upon microscopical examination is a thickening of the walls of 
the blood-vessels, surrounded by a zone of proliferated glia tissue of 
irregular width and arrangement. The vessels may be thickened by 
hyaline degeneration, and the productive changes with the degeneration 
lead to narrowing of the lumen. The perivascular lymphatic space is 
often filled with cells containing droplets that stain black with osmic 
acid. Occasionally the vessels appear to be increased in number, 
although this is possibly due to contraction of the surrounding tissue 
bringing them more closely together. In the center of the foci the 
neuroglia cells are not markedly increased; in the periphery, however, 
they seem to have undergone a distinct hyperplasia. The neuroglia 
fibers throughout are somewhat thicker and more irregular, and form a 
large-meshed network. In the midst of the neuroglia compound 
granular cells and amyloid bodies are often found. If stained by 
Weigert's method, it is at once evident that the myelin-sheaths have 
disappeared almost entirely, all the sclerotic areas appearing bright 
yellow. If the Marchi method be used, however, a certain number 
of degenerated myelin-sheaths will be found, as a rule, still present. 
The edge of the sclerotic area does not end as sharply as appears macro- 
scopically, but gradually fades into the healthy tissue. The axis- 
cylinders, in spite of the destruction of the myelin-sheaths, are nearly 
always present and apparently normal, a fact which explains the 
absence of secondary degeneration beyond the lesions. In those situations 
where the hyperplasia of the neuroglia fibers is most pronounced, the 
axis-cylinders may be swollen or show partial fatty degeneration, or be 
entirely absent. The ganglion-cells are shrunken and pigmented, and 
may, in rare cases, completely disappear. In advanced cases of the 
disease the process resembles more closely a chronic myelitis; the axis- 
cylinders passing through the lesion may be totally destroyed and 
secondary degeneration occur. In those cases that have been studied 
in the early stages of the process perivascular inflammatory changes 
have been present, and it is about these that the sclerotic areas have 



916 



A TEXT-BOOK OF PATHOLOGY 



formed. In some cases thrombi have been also detected in the ves- 
sels, and many of them show the early stages of hyaline degeneration. 
For this reason, and because disseminated sclerosis frequently develops 
after an infectious disease, it is generally accepted that the process is 
due to infectious embolism. Certain authors, however, hold that the 
vessels are not the primary origin of the disease, as in many of the 
sclerotic foci they are perfectly healthy. 

General Progressive Paralysis. — Paresis. — There has been much 
diversity of opinion concerning the true nature of general progressive 
paralysis. The lesions hitherto described have varied in nature and 
situation. Nevertheless, there seems to be good reason to accept an 
infectious origin of the disease, and unquestionably the symptomatology 
and, to a certain extent, the morbid changes indicate that the brain is 
the organ chiefly involved. 

The etiology is not yet clear, but some assistance has lately been 
produced by the finding by Noguchi of the Spirochceta pallida in the 
brain of paretics. He has succeeded in showing the presence of these 
spirals in a goodly proportion of cases, in a few instances in enormous 
numbers, not only in the brain, but in the cord, especially of tabetics. 
Clinically, it is difficult in many cases to get a history of syphilis, but 
this disease is certainly the more important factor in the causation of 
paresis. It is a disease of any age past adolescence, and has been seen 
in the very young. The Wassermann test is positive in a vast majority 
of the cases. 

The changes found most frequently are as follows: the dura mater 
is adherent to the skull; it may be thickened, and often shows upon its 
under surface the exudate of a hemorrhagic pachymeningitis. The 
arachnoid is thickened and opaque, particularly along the course of the 
veins; and in the subarachnoid space there is often a considerable 
effusion of liquid. The pia mater is thickened and opaque and may or 
may not be adherent to the cortex; in the latter case the subpial areolar 
tissue is distended with fluid. Microscopically, there is often found a 
round-cell infiltration about the blood-vessels; their walls are thickened 
and show some hyaline degeneration. The fluid in the areolar spaces 
may be clear, or, as is more commonly the case, it is viscid and even 
colloid in nature. The gross appearance of the brain is frequently con- 
siderably altered. The convolutions are flattened; the sulci broader 
than normal; the consistency of the brain is slightly increased; the 
cortex is usually pale and greatly reduced in thickness. The white 
matter may appear to be slightly looser in texture, but ordinarily 
presents no change. Microscopically, the blood-vessels in the cortex 
have thickened walls, and occasionally one is found with a completely 
obliterated lumen. There is usually distention of the perivascular 
spaces, which may be filled with round cells and various products of 
degeneration, such as pigment granules. The glia-cells are greatly 
increased in number, although it is difficult to decide whether this is 
absolute or relative. The neuroglia fibers are usually slightly coarser 
than normal. The tangential fibers of the cortex may be reduced in 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



917 



number or entirely absent. The ganglion-eells exhibit a great variety of 
alterations. The protoplasmic processes are varicose, and when suffi- 
ciently well impregnated show the absence of the gemmules. The 
axis-cylinder is usually distinct, due to the degeneration of the myelin- 
sheath. The body of the cell may be irregular and vacuolated, and there 
is often extensive chromatolysis. The ventricles of the brain are usually 
slightly distended, probably the result of simple atrophy, and the 
choroid plexus is often cystic. Changes are frequently found in the 
spinal cord. The ganglion-cells in all parts show pronounced degen- 
erative characteristics. This is particularly interesting in view of the 
fact that the motor symptoms progress so gradually. The posterior 
roots are often slightly degenerated, and there is systemic degeneration 
of the posterior columns not unlike that found in the early stages of 
tabes dorsalis, excepting that ordinarily it is most pronounced in the 
cervical region. The pia and arachnoid of the cord, particularly those 
portions covering the posterior columns, are thickened and more or less 
adherent. The dura is often markedly thickened and may exhibit 
pachymeningitis. 

INJURIES TO THE CENTRAL NERVOUS SYSTEM 

Injuries to the central nervous system produce a great variety 
of lesions, according to their nature and severity. 

Concussion ; either from a single shock or from repeated blows, may 
give rise to transient or permanent changes. Ordinarily there is con- 
siderable hemorrhage at the site of the blow. This may be either be- 
tween the dura and the skull or between the arachnoid and the pia. 
Small hemorrhages are not infrequently found in the central nervous 
substance, and appear to occur particularly in the direct line of the 
force applied to the skull. In the latter case autopsies have shown the 
existence sometimes of multiple hemorrhages, sometimes of disseminated 
areas of sclerosis in the white and the gray substances. Not infre- 
quently hemorrhage is also found in the subarachnoid space of the 
opposite side (hemorrhage by contre coup). This is explained either by 
supposing a flattening of the elastic skull or by ascribing it to the force 
with which the brain rebounds against that side. Occasionally in the 
spinal cord, after experimental repeated concussions, changes somewhat 
systemic in character and affecting chiefly the posterior columns have 
been observed. The hemorrhages may be punctate or, in some cases, par- 
ticularly if the injury is severe and the arteries are diseased, massive. 

Lacerated wounds of the brain are usually produced by fracture of 
the skull. There is extensive interstitial hemorrhage and softening, 
and the surrounding tissue is edematous. If only subdural hemorrhage 
occurs, it may produce compression with secondary yellow softening. 
Any of these lesions may heal with the formation of a scar and the pro- 
duction of more or less extensive secondary degeneration. Extensive 
lacerations of the brain are sometimes the result of injury during birth, 
giving rise to so-called cerebral palsies of childhood. In these cases, 



918 



A TEXT-BOOK OF PATHOLOGY 



as the central nervous system is not fully developed when the injury 
occurs, there is hypoplasia of the affected parts. 

Punctate wounds of the brain are due to fragments of bone, to sharp 
instruments, or to bullets. In nearly all cases a certain amount of 
infection occurs, giving rise to encephalitis. The injured area usually 
undergoes complete necrosis, and this extends for some distance into 
the surrounding tissues. The necrotic area is composed of a granular 
detritus, in the midst of which are found altered blood-pigment and 
broken-down nuclei. At the periphery there is usually some granulation 
tissue, proliferation of the neuroglia, and more or less round-cell infil- 
tration, according to the intensity of the inflammatory process. Experi- 
mental lesions may be produced in various ways, the most interesting 
results, perhaps, being those found after the introduction of foreign 
bodies or after careful aseptic laceration. In either case, shortly after 
the operation, necrotic changes will be found in the injured area. There 
is marked proliferation of the neuroglia cells, even as early as the third 
day, and of the neuroglia fibers. New capillaries may be seen pushing 
into the area, the endothelial cells of their walls exhibiting karyokinetic 
figures. The nervous tissue in the immediate neighborhood is in various 
stages of degeneration. If there has been much hemorrhage, the blood- 
pigment will be found in irregular homogeneous masses or in the form of 
hematoidin crystals. Later, evidences of regeneration in the nervous 
tissue may be observed, particularly the appearance of karyokinetic 
figures in the nuclei of the ganglion-cells. The injured area is ultimately 
replaced by a mass of coarse neuroglia fibers containing, usually, fewer 
cells than normal. That true regeneration of the central nervous 
system ever occurs in the human body is exceedingly doubtful; indeed, 
it is not certain that it occurs in any of the vertebrates, although after 
removal of the tail in lizards a spongy mass of neuroglia may be found 
in the new organ. 

Compression of the brain is due to tumors or to various infiltrative 
and exudative processes more or less localized. The most common are 
those occurring from hemorrhage between the skull and dura, or between 
the latter and the pia. (See Concussion.) The effect is to compress 
the gyri, causing interference with their function, blood-supply, and 
nutrition. The foreign mass may be partly absorbed, but usually 
something remains, like a cyst with thickening of the meninges, press- 
ing into the brain substance, with the formation of concavities of 
various shapes (traumatic porencephaly). 

INFECTIOUS DISEASES 

Tuberculosis occurs in the brain in the form of miliary tubercles 
or as large masses, the so-called solitary tubercle, or tyroma. 

The condition is always secondary and comes through the blood- 
stream or by extension (bone), usually the former. 

Miliary tubercles are met with in association with tuberculous 
meningitis. They are most frequent at the base of the brain. 



DISEASES OF THE BRAIN AND* ITS MEMBRANES 



919 



Solitary tubercles occur independently of tuberculosis of the men- 
inges. They are more frequent in children than in adults, and usually 
occur in cases in which there is tuberculosis of other parts of the body, 
notably the lymphatic glands. The infection reaches the brain through 
the blood-vessels. The lesions are rounded masses of grayish or yellow- 
ish color, sometimes showing fresh gray tubercles at the periphery. 
The growth of the mass is caused by increase in size of the original 
tubercles with inclusion of new-formed tubercles at the periphery. 
Early caseation is usual. Secondary infection of the pia sometimes 
occurs. 

Occasionally there is a sclerosis in the vicinity of the large mass, 
arising from glia proliferation or from fibrous tissue in the adventitia 
of blood-vessels. 

Syphilis appears in the brain in the form of gummata or as a diffuse 
vascular disease with secondary degenerative conditions. 

Gummata usually begin in the subarachnoid space, originating in the 
membranes and involving the brain substance secondarily. The dura 
may be simultaneously involved, and the three membranes may be 
adherent to each other and firmly attached to the brain. Primary 
gumma of the brain substance is certainly very rare. In the earlier 
stages the gumma is a grayish and rather translucent growth, but 
secondary caseation occurs so rapidly that the primary stage is rarely 
observed. As a rule, the lesion appears in the form of an irregular, dry, 
caseous area occupying the cortical portion of the brain and attached 
to the pia and arachnoid, and even the dura. The cerebral substance 
surrounding the growth is more or less softened and degenerated. 
The blood-vessels in the affected area or its vicinity are the seat of 
endarteritis, which in some causes complete occlusion of the lumen. 
In hereditary syphilis symmetric gummata of the brain are occasionally 
found. 

Syphilitic disease of the blood-vessels of the brain takes the form 
of more or less diffuse peri- and endarteritis. Secondary degenerations 
and softening, or sclerosis, of a diffuse or focal character, may result 
from the vascular disease, but neither these changes nor the vascular 
changes are peculiar and distinctive. 

Actinomycosis of the brain is generally secondary to actinomycosis 
of the tissues of the neck, and results from extension upward through 
the base of the skull. The membranes are first involved, the brain 
substance secondarily. The lesion may take the form of a chronic 
abscess or may be tumor-like in appearance. 

TUMORS 

The most common is probably glioma, but almost equally as common 
is sarcoma. Cholesteatoma, lipoma, endothelioma, and teratoid cysts 
also occur, but they spring from the membranes and have been de- 
scribed in connection with them. 

Glioma usually appears as an infiltrating mass, causing little 
alteration in the structure of the brain, somewhat harder in consistency 



920 



A TEXT-BOOK OF PATHOLOGY 



than the brain substance and slightly darker. It is rarely a multiple 
growth, and shows no marked predilection for any particular portion of 
the brain, although it occurs more frequently in the cerebral hemispheres 
than in the basal ganglia or the cerebellum. It always springs from the 
neurogliar tissue of the central nervous system, and is remarkable for 
its extreme richness in cells, that by suitable staining methods may be 
shown to possess protoplasmic processes {astrocytes). These proto- 
plasmic processes, either wholly or in part, form the so-called matrix 
of the tumor, which appears to be composed of numerous fine, inter- 
lacing fibers, in the midst of which, by the ordinary staining methods, 
the cell appears to lie. Usually, the tumor is exceedingly vascular, 
the vessels consisting of small capillaries or larger spaces lined with 
endothelium, and this vascularization may be so excessive that the 
tumor in parts has a delicate pinkish or reddish color, giving to the 
cross-section a mottled appearance. In some cases the consistency 
of the tumor is quite hard, and in these the cellular elements are de- 
creased in amount proportionately to the fibrous tissue. Ordinarily 
true nervous tissue is absent from the midst of the tumor, the mass in 
the center being made up of the neuroglia tissue. This gradually 
diminishes toward the periphery, and ultimately fades into the true 
nervous tissue that may be somewhat edematous. In some cases, 
however, as in ordinary sclerosis of the central nervous system, myelin- 
ated nerve-fibers may be found in the midst of the tumor, and it fre- 
quently happens that the secondary degeneration extending from a 
glioma is much slighter than the apparent extent of the process would 
lead one to expect. Occasionally, either glioma cells, or possibly 
ganglion-cells, that have undergone proliferative changes in the midst 
of the growth, may be found. These are much larger than the ordinary 
cells, and contain numerous branched processes and often one or several 
large nuclei. This is the so-called ganglionar neuroglioma. 

Some pathologists hold that the starting-point of glioma is always 
one or more ependymal cells that have been displaced in embryonal 
existence and have failed to assume the type of glia-cells, basing their 
theory in part upon the atypical shape of many of the glioma-cells. 
Sometimes the cells of gliomata arrange themselves in rosettes, as if 
forming the lining of a channel. These have been interpreted as remains 
of embryonic ependymal structures, and the name neuro-epithelioma 
applied when such formations are numerous; these tumors have been 
found in specialized nervous tissue like the retina. 

Sarcoma of the brain is probably the next most frequent tumor. 
It usually occurs in middle adult life, although it is quite frequent in 
children. The commonest seat is the cortex, which it probably invades 
from a primary focus of proliferation in the membranes. The tumors 
are ordinarily nodular growths, usually distinctly circumscribed from 
the surrounding tissue, and in some cases even surrounded by a fibrous 
capsule, from which they can be readily removed. They are rather 
firmer than the brain tissue, and sometimes slightly umbilicated if at 
the surface. The surface of section is pale and dry, but frequently 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



921 



mottled on account of the presence of hemorrhages. If primary, the 
sarcomata are single; if secondary, more frequently multiple. Histo- 
logically, almost any type of sarcoma may be found, the most frequent 
perhaps being the round-cell, non-pigmented form. Giant cells are 
very frequently found. Ordinarily the tumors are extremely vascular, 
and occasionally contain interstitial hemorrhages. The surrounding 
brain tissue shows the symptoms of marked compression, is edematous, 
and may contain small interstitial hemorrhages. The true nervous 
substance is ordinarily degenerated, and we find extensive secondary 
degeneration as a result of the presence of the tumor. 

Many authors believe that a combination of glioma and sarcoma 
may occur, and gliosarcomata have been frequently described. As 
the neuroglia tissue has the functions of connective tissue, and in many 




Fig. 428. — Psammoma, showing calcareous spicules and whorls. 

respects resembles it in its pathological processes, it is natural that a 
glioma should be similar to a sarcoma, and this has possibly caused an 
error of diagnosis in some cases. As the two tumors arise from tissue of 
different natures and develop in different situations their combination 
is theoretically unlikely. 

Certain forms of tumors have been described that appear to spring 
from the adventitia of the bloodrvessels. They consist of masses of 
cells usually sharply circumscribed, somewhat cylindrical in shape, 
having in their center a small lumen in which blood-cells may some- 
times be detected. These are the so-called 'perithelioma or angiosarcoma. 
Such tumors in all probability come from the meninges in most cases. 

Fibroma occurs as a hard, circumscribed tumor, sometimes found 
in the hemispheres, but it is extremely rare. 

Lymphangioma appears to arise from the pia. 



922 



A TEXT-BOOK OF PATHOLOGY 



Osteoma is usually an extension inward from the skull or mem- 
branes, but occasionally occurs as a tumor, apparently originating 
in the brain substance, forming hard masses from the size of a pea 
to that of a cherry, and somewhat irregular in shape. 

Psammoma. — This special term has been given to tumors con- 
taining calcareous granules. It has been mentioned in connection 
with the choroid plexus and the membranes! Occasionally circum- 
scribed fibrous tumors containing calcareous granules are found in the 
brain substance, but these are extremely rare (Fig. 428). 

Carcinoma of the substance of the brain is invariably a metastatic 
growth. It appears either as small, round, circumscribed nodules, of 
firm consistency and pale color; or as larger, more or less infiltrating 
masses with softened interior. It usually replaces entirely the nervous 
tissue, either pushing it aside or destroying it, and gives rise, therefore, 
to more or less pronounced secondary degeneration. Multiple metas- 
tatic carcinomatous growths, however, may exist in the brain without 
causing clinical symptoms. 

THE CHOROID PLEXUS 

The choroid plexus consists of a plexus of vessels derived from 
the mesoblast, that are everywhere covered by a layer of cuboidal or 
columnar epithelium. Histologically, it consists of an inner layer of 
endothelial cells and an outer layer of epithelial cells, separated by a 
small amount of areolar fibrous tissue. The structure of the choroid 
plexus, therefore, bears a very close resemblance to the structure of the 
glomeruli of the kidneys, and, as it is obvious that the blood-vessels of 
which it is composed can have no nutritive function, excepting in so far 
as they supply the epithelium that covers them, it has been supposed 
that the choroid plexus is a secretory organ, its object being to secrete 
the cerebrospinal fluid. This theory is sustained by the facts that the 
cerebrospinal fluid differs in composition from the lymph, or from the 
fluid poured out in serous exudations, and that extracts of the choroid 
plexus will stimulate the secretion of the fluid in experimental animals. 
The choroid plexus probably also acts as a barrier to the entrance of 
toxic substances to the spinal fluid. 

Hypersecretion. — In certain cases in which communication between 
the cavities of the brain and the exterior exists — as, for example, through 
the ethmoid plate of the nose — there is distinct hypersecretion of the 
cerebrospinal fluid. In a case described by St. Clair Thomson as 
much as a pint was discharged in twenty-four hours. In these cases, if 
for any reason the flow is checked, symptoms of intracranial pressure 
occur. Regarding the pathological changes in the choroid plexus that 
are associated with this condition we have at present no information. 
Hypersecretion probably also takes place in all inflammatory conditions. 

Inflammation. — In inflammatory conditions, particularly meningitis, 
encephalomyelitis, either separate or combined, and associated with the 
presence of an abnormal quantity of albumin in the cerebrospinal fluid, 
more or less inflammation of the choroid plexus is usually found. This 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



923 



is indicated particularly by round-cell infiltration about the vessels 
and beneath the epithelium. Sometimes there is a slight amount of 
exudation upon the epithelial surface, and occasionally small foci of 
suppuration can be detected. 

Infectious Diseases. — Among the infectious diseases the only one 
of importance is tuberculosis. In this condition miliary tubercles or 
large cheesy foci may be found. 

Chronic inflammation appears to be exceedingly rare, or, what is 
probably more accurate, has rarely been described, for there is every 
reason to believe that the choroid plexus shares in all conditions that 
involve the pia mater. Atheromatous conditions seem to be very 
infrequent, but a certain amount of thickening of the walls of the vessels 
may be observed in old age. A certain amount of overgrowth of con- 
nective tissue, sometimes associated with slight round-cell infiltration, 
is also occasionally found in old people. 

Hemorrhage may take place into the choroid plexus, and is usually 
an agonal phenomenon. 

Degenerations. — Calcification is the most frequent of the infiltra- 
tions. This may be recognized by the gritty sensation upon cutting 
into the choroid plexus. Microscopically, the calcareous nodules 
appear as minute dark granules that stain purplish with hematoxylin. 
Masses of cholesterin are by no means uncommon; they rarely present 
the form of typical cholesterin plates, but are somewhat irregular in 
outline, of a faint yellowish color, and shine brightly when examined by 
oblique light. Both conditions are common in old people. 

Pigmentary infiltration probably also occurs, certainly in malaria, 
and perhaps in old age. 

Ependymitis of ventricles may be chronic or acute. The acute 
form is always secondary to meningitis, and is characterized by prolifer- 
ation of the ependymal cells and the usual inflammatory changes. 
Chronic ependymitis is usually associated with sclerosis of the brain. 
The surface is granular or even nodular. The ependyma is thrown into 
folds, and there is great proliferation of the subependymal neurogliar 
fibers (Fig. 429). 

Tumors. — A great variety of tumors occurs in the plexus. Cysts 
may be either retention or extravasation cysts, or parasitic. The 
retention cysts may be lined with epithelium, and probably represent 
adhesions at the edges of fissures with persistence of secretory activity. 
More commonly they are lined with endothelium and represent dilated 
lymph-spaces. They may be single or multiple, and appear as small 
translucent sacs, filled with a clear, slightly yellowish liquid, or else a 
colloid-like, viscid mass. Parasitic cysts are usually due to Tcenia 
solium.. They may be either single, the Cysticercus cellulosce, which may 
be attached to the plexus or lie free in the ventricular cavity, or multiple, 
forming the so-called Cysticercus racemosa of the brain. 

Among the benign tumors, fibromata, possibly only organized thrombi, 
and lipomata have been described. A dermoid cyst has been reported by 
Lebert. Endotheliomata may spring from the lymphatic spaces. Epi- 



924 



A TEXT-BOOK OF PATHOLOGY 



theliomata, or ependymoma, may arise from the epithelial covering. 
Two varieties have been described: the papillomatous and cylindrical 
cell tumor. These tumors are rarely uniform in character or pure in cell 
content; they are apt to show solid and cystic areas, and to contain 
some nervous tissue elements. They are usually single growths and 
do not give metastases. 

The cerebrospinal, or arachnoid, fluid is a clear, limpid, colorless 
or slightly yellow liquid occupying the meshes of the arachnoid, the sub- 
dural space, and the free cavities of the central nervous system. It is 
said to vary in amount from 50 to 100 c.c, but only a small portion is 
obtained by spinal puncture. It is faintly alkaline in reaction and 
salty in taste; its specific gravity is about 1008, varying slightly in 
health and but little in disease, except when the liquid is distinctly 
purulent, it then being notably heavier. The fluid is produced by 
filtration through the choroid plexus by filtration and by the secretory 




Fig. 429. — Sclerotic nodule in the floor of the lateral ventricle, with wrinkling of the 

ependyma; X 100 (Sailer). 

power of this organ, by the perivascular tissue of the nervous system, 
and possibly by the arachnoid villi. It returns to the circulation via 
the last, and by way of the veins and lymphatics. Its accumulation 
in disease is due to overaction of the sources by congestion and to 
obstruction to its escape by inflammatory lesions of the meninges. In 
health the fluid contains a small quantity of globulin, nucleoprotein, 
albumose, and urea; a reducing body is also usually present. Under 
pathological conditions any or all of these may be increased. The cells 
of the fluid are only mononuclear, lymphocytic and endothelial, during 
health, and are about 10 per cubic centimeter. The fluid, as deter- 
mined by measurement in the spinal column, has a pressure of about 
120 to 160 mm. The functions of the cerebrospinal fluid are to act as 
a mechanical support and protection to the central nervous system, 
and it may be a medium of metabolic activity for the superficial parts 
of the brain. 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



925 



In disease so many modifications are possible that only the most 
characteristic can be given for the various important conditions. So far 
as quantity is concerned, the only change seems to be in the direction of 
increase. This is brought about by inflammatory lesions, decrease of 
blood-pressure, or to venous obstruction. Within the ventricles in- 
crease of the fluid and its pressure are caused by an obstruction to the 
passage of fluid from the ventricles and aqueduct of Sylvius through 
the foramen of Magendie. 

Cerebrospinal meningitis of the epidemic form shows in early stages a 
cloudy fluid, but soon a distinctly purulent character is assumed. Cells 
up to many thousands per cubic centimeter are found. Micro-organisms 
are found within the cells and free in the fluid. Protein contents are 
naturally much increased. The pressure may rise to 250 mm. Menin- 
gitis of pneumococcus origin will give similar conditions, while in 
influenzal cases the fluid is not rarely hemorrhagic, or at least blood 
tinged. 

Tuberculous meningitis gives, as a rule, an excessive, clear fluid in 
which a delicate coagulum will form on standing; occasionally the fluid 
is turbid. The pressure is increased to a variable extent. Protein 
is increased as is the cellular content; mononuclears usually predominate, 
but polynuclears may be numerous. 

Paresis and Tabes. — In these conditions the amount of the cerebro- 
spinal fluid is usually increased, but not always, and the significant 
features are a pronounced increase in mononuclears and an excess of 
globulin. The fluid may also contain the antigen of syphilis and may 
be used in the Wassermann test. 

Poliomyelitis. — In the very early stages the fluid may be slightly 
turbid, but it shortly becomes clear; occasionally spontaneous coagula- 
tion with a very faintly cloudy clot is seen. The protein, globulin, is 
increased early in the disease and usually remains in excess throughout 
the attack. No great excess of cells is found; polynuclears may be as 
numerous as mononuclears. The • fluid in poliomyelitis is in great 
excess, and may be as high in pressure as in pyogenic inflammatory 
diseases. It rarely contains the virus. 

Trypanosomiasis gives an excess of clear or slightly turbid spinal 
fluid in which an increase of mononuclears and of the globulin may be 
found; the trypanosomes may also be present. 

The Spirochceta pallida has been found in the fluid in cases of 
active nervous system syphilis. 

Hydrocephalus. — Excess in quantity of the cerebrospinal fluid in 
the ventricles is known as hydrocephalus. This may be produced by a 
great variety of causes. It may be congenital and perhaps due to a 
malformation, but is more often a result of disease. Congenital hydro- 
cephalus frequently appears to be due to some defect on the part of the 
parent, and is particularly common in the children of drunkards. 

Congenital hydrocephalus internus is characterized by a gradual 
accumulation of cerebrospinal fluid in the lateral and third ventricles 
of the brain, probably the result of excessive secretion from the choroid 



926 



A TEXT-BOOK OF PATHOLOGY 



plexus, with some anomalous formation to prevent its escape or ab- 
sorption (Fig. 430). As a general rule, the fourth ventricle is not involved. 
The aqueduct of Sylvius, however, is often dilated. Sometimes the 
fifth ventricle is distended or the septum has atrophied and disappeared, 
allowing free communication between the two lateral ventricles. Less 
frequently the infundibulum is distended and forms a small sac at the 
base of the brain. Usually the disease is manifest at the time of birth, 
and the head may even at this period have attained the circumference 
of more than 50 cm. Externally, the head is spherical and large; the 
face is small, and, with the bulging forehead, gives to these patients a 
characteristic expression. The cranial bones are usually more or less 

separated; frequently the edges of the 
sutures are an inch or more apart. The 
anterior fontanel is large and usually bulg- 
ing. If the bones of such a skull be ex- 
amined, it will usually be found that they 
are very thin and that ossification is in- 
complete. The dura mater is tense, and 
beneath it may be found the greatly flat- 
tened convolutions. The brain substance 
seems softer ; often there is distinct fluctua- 
tion, although the brain collapses as soon 
as it is removed from the cranial cavity. 
The distance from the wall of the ventricle 
to the surface is much less than normal, 
this atrophy seeming to affect the white 
substance more than the cortex. The total 
weight of the brain, however, is often nor- 
mal or nearly so, and it is impossible to say 
that an actual atrophy has really taken 
place. The substance of the brain is 
pale, probably as a result of the pres- 
sure, and often softened, particularly in 
Fig. 430.— Congenital inter- the neighborhood of the ventricles, al- 

nal hydrocephalus, with marked ,1 1 ,v • 1 1 1 1 n 

atrophy of the white substance though this is probably only an unusually 
(from Bollinger). rapid postmortem change. The floor of 

the ventricles may be smooth or slightly 
roughened, and occasionally distinct nodules may be observed. In the 
latter case there is usually considerable proliferation of the neuroglia 
in the cortex, and just beneath the floor of the ventricle a sort of sclerosis 
of the brain substance. The cerebrospinal fluid is usually clear and not 
abnormal in consistency. Occasionally, however, it is somewhat turbid, 
particularly if there are any signs of old inflammatory action. The 
choroid plexus is often somewhat enlarged, pale, and may contain cysts. 
As the patients increase in age there is usually considerable increase in 
size of the head; nevertheless, the convolutions gradually become more 
rounded and the white substance appears to undergo a sort of redevelop- 
ment, for the layer of brain tissue between the ventricle and the surface 




DISEASES OF THE BRAIN AND ITS MEMBRANES 



927 



becomes thicker. Systemic degenerations of the white fibers are un- 
common. There may, however, be marked thinning of the corpus 
callosum and the anterior commissure. Cases have been described in 
which a descending degeneration along the pyramidal columns was found 
in the cord. 

Partial hydrocephalus has been described. It is probably, in the 
great majority of cases, of congenital origin. It may affect only one 
ventricle, or even only a part of a ventricle, as, for example, the anterior 
or posterior horn of one of the lateral ventricles. It appears to be the 
result of an obliteration of one of the normal passages by which the 
ventricles communicate with one another. 

External hydrocephalus is the accumulation of fluid that occurs 
in the subarachnoid space to replace brain tissue that has undergone 
atrophy, or to fill the cavities in porencephaly. Occasionally sym- 
metrical collections of liquid are found, as in a brain removed from an 
idiot, in which both temporosphenoidal lobes were excavated and 
replaced by large cysts. 

Acquired hydrocephalus may be either acute or chronic. The 
acute forms are usually secondary to inflammatory changes in the 
meninges, extending to the choroid plexus and to the ependyma, or are 
caused by some abnormal growth pressing upon the veins of Galen, 
or to obstruction of the aqueduct of Sylvius or the foramen of Magendii. 
In the atrophic brains of the aged dilated ventricles are frequently found. 

Acute acquired internal hydrocephalus is usually the result of acute 
basilar meningitis, either inflammatory or tuberculous. The brain, 
in addition to the changes in the meninges, presents all the character- 
istics of intense intracranial pressure. The convolutions are flattened 
and pale. The brain tissue is usually soft, or at least softens rapidly 
after death, particularly the part that surrounds the distended ven- 
tricles. Upon opening the brain the fluid is usually found under con- 
siderable pressure, and often almost gelatinous in consistency. Fre- 
quently, microscopical examination of the brain substance will show the 
presence of acute, disseminated, suppurative encephalitis. The ep- 
endyma of the ventricles is injected and often covered with lymph. 
In the tuberculous form it may be roughened, as a result of the presence 
of numerous miliary tubercles. The choroid plexus is injected; in the 
acute forms it also has some lymph upon the surface, and in the tuber- 
culous form may contain miliary tubercles. 

Chronic hydrocephalus is usually a late result of meningitis, particu- 
larly the epidemic form. Occasionally it is the result of gradual com- 
pression of the veins of Galen, or obstruction to the course of the liquid 
from the lateral ventricles to the subdural space, as, for example, by a 
tumor of the cerebellum. Perhaps most frequently it is the result of 
a chronic granular ependymitis. In these cases the distention is more 
pronounced than in the acute form. The ependyma is thickened and 
opaque, and often contains small hard nodules. Occasionally, bands 
of organized fibers may be found in the cavity of the ventricle. 



CHAPTER XIII 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 

The Dura Mater 

Diseases External to the Dura Mater. — Among the minor proc- 
esses that may occur externally to the spinal dura mater is fatty infil- 
tration, sometimes associated with general obesity, but occasionally 
found in patients that are moderately emaciated. 

Hemorrhage may occur on the external surface of the dura, the 
blood being found distributed in the extradural areolar tissue. The 
usual cause is traumatism, but it may also occur in convulsive condi- 
tions. Ordinarily, the blood remains circumscribed and forms a spinal 
hematoma; rarely, a cyst results. 

Diseases of the Dura Itself. — Most of the pathological processes 
are secondary to some disease of the vertebral column. The most 
important is tuberculosis; this gives rise to external tuberculous pachy- 
meningitis, characterized by a collection of cheesy material which may 
have undergone either softening or necrosis, or else contains pus-cells. 
The dura in the affected region is usually considerably thickened, and 
may have upon its inner surface a slight amount of exudate. The char- 




Fig. 431. — Tuberculous pachymeningitis secondary to spinal caries. 



acter of the lesions is not different from that of tuberculosis in other 
serous membranes (Fig. 431). 

Pachymeningitis cervicalis is a localized tuberculosis or syphilis 
of the dura mater occurring in the cervical region, and characterized 
by considerable thickening, sometimes amounting to \ cm. or more. 
The dura is usually adherent to the spinal canal and to the arachnoid 
and pia, the latter showing more or less involvement. The serious 
changes consist of compression of the roots and of the spinal cord, the 
latter especially in the anteroposterior direction. The process may 
extend into the substance of the cord and produce a myelitis of the 
periphery, and occasionally extends deeper and causes more or less 
extensive secondary degenerations. 

928 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 929 



Of the acute inflammations the most important is internal hemor- 
rhagic pachymeningitis, a process similar to that occurring in the dura 
mater of the brain. It consists of a layer of granulation tissue in which 
many of the capillaries have ruptured, giving it a more or less uniform 
reddish appearance; it is somewhat irregular in outline and of varied 
extent, and not infrequently adhesions form between the dura and the 
arachnoid. 

Syphilis occurs either in the form of discrete gummata or as a regular 
and diffuse thickening of the inner layer. 

Tumors of the dura are rare, but when present grow inward, com- 
pressing the cord and giving symptoms of transverse localized disease. 
Tumors from the spinal canal frequently invade the dura. 

Lipoma is the commonest benign tumor. Myxomata and fibroviata 
are exceedingly rare. Chondroma has been observed. 

Sarcoma may be of the round-cell, angiomatous, or alveolar type. 
It is usually irregular in outline, spreading like a fungous mass over 
the surface of the membrane, which exhibits fibrous thickening. If 
small and occurring on the anterior aspect, it may produce no symp- 
toms whatever. In this situation it is frequently secondary. In a 
few rare instances melanotic sarcoma has been observed. Not in- 
frequently a granular sarcomatous mass invades the cauda equina 
and infiltrates it for a considerable distance downward. The nerve- 
roots often fail to show any signs of degeneration, and apparently no 
pressure symptoms are produced. In some cases sarcomata of the dura 
produce proliferation of the neuroglia tissue in the adjacent portion 
of the spinal cord. 

Upon the inner surface a variety of tumors have been observed. 
Horsley mentions myxomata, fibromata, carcinomata, and sarcomata. 
In rare cases echinococcus cysts have been observed, and even the 
cysticercus. 

The Pia-arachnoid 

circulatory disturbances 

Active hyperemia precedes and accompanies inflammatory changes. 
It is rarely seen postmortem, and in the majority of cases its existence 
can only be inferred. 

Passive hyperemia is very common — that is to say, in many 
cases the veins of the pia mater are found to be tortuous and greatly 
distended with blood. This is usually due to postmortem hypostasis. 

Hemorrhage may occur from traumatism or the rupture of small 
aneurysms, the most frequent place for the latter being the cervical or 
basilar region. 

DEGENERATIONS 

Calcareous infiltration sometimes occurs, appearing as small, 
hard plates, rarely more than 0.5 cm. in diameter, scattered along the 
whole length of the spinal cord. It is probably always secondary to 
inflammatory processes, as spinal syphilis and tuberculosis. 

59 



930 



A TEXT-BOOK OF PATHOLOGY 



INFLAMMATIONS 

Acute inflammation, or acute leptomeningitis, is often second- 
ary to cerebral meningitis. It may occur, however, independently as 
a result of local suppurative processes, particularly those of the spinal 
column. It may be serous or purulent in character, and in the latter 
an exudate is found upon the inner surface of the dura and in the sub- 
arachnoid space, often extending the entire length of the spinal cord. 
The microscopical changes are essentially similar to those found in the 
membranes of the brain. Involvement of the cord is, however, much 
more common. There is usually extensive round-cell infiltration in the 
anterior commissure and small foci of round cells scattered throughout 
the gray and the white matter, especially in the latter. Frequently 
these can be seen to surround a blood-vessel, but this is not always the 
case, and it is not unlikely that purulent material can enter from the 
lymphatics of the pia. The covering and interstices of the nerve-roots 
are commonly infiltrated. If death does not occur, adhesions may form 
between the dura and arachnoid, but these are certainly exceedingly 
uncommon in the cord. 

Chronic leptomeningitis is usually associated with sclerosis of 
the spinal cord; thus, in locomotor ataxia the pia mater over the poste- 
rior column may be opaque and slightly thickened. It may also be 
consecutive to some of the other inflammatory processes, and in this 
form adhesions may be found between the dura and arachnoid (pachy- 
meningitis and arachnitis adhesiva). 

In cases of injury of the spinal column, such as fracture, caries, etc., 
in which continuous pressure is produced upon the dura mater, it be- 
comes thickened and adherent to the bone and to the pia and may 
cause pressure upon the spinal cord. In these cases there is rarely any 
round-cell infiltration in the thickened dura, which consists almost en- 
tirely of fibrous connective tissue and blood-vessels; the latter have 
greatly thickened walls. 

INFECTIOUS DISEASES 

Tuberculosis may occur in the form of miliary nodules or as small 
cheesy masses, usually extending a slight distance from the pia mater 
into the substance of the cord. It is disputed whether an acute lepto- 
meningitis without miliary or cheesy nodules may be caused by this 
organism alone, but, while it is probable that such inflammation 
may occur, this has not as yet been, definitely established. Solitary 
tubercles may occur in any part of the spinal cord. They are rarely 
encapsulated. Tuberculous meningitis is hematogenic, or arises by 
extension. The localized form is commonly the result of Pott's dis- 
ease. A generalized form occurs in connection with cerebral menin- 
gitis (q. v.). 

Syphilis appears as a thickening of the membranes with multiple 
gummata, often projecting into the substance of the cord or extending 
to and involving the dura mater. The vascular changes are very char- 



DISEASES OP THE SPINAL CORD AND ITS MEMBRANES 931 



acteristic; nearly all the blood-vessels exhibit the typical round-cell 
infiltration and thickening of the intima which have been described in 
the section on endarteritis syphilitica. There are also a perivascular 
round-cell infiltration and some proliferation of the adventitia. The 
veins may also be involved. The lumen of both sets of vessels is usually 
contracted, and there is a great tendency to the formation of thrombi. 
In these thrombi organization may take place, with the formation of 
new blood-vessels. The spinal cord may also exhibit various lesions, 
due either to pressure or to direct extension inward from the pia. 

In congenital syphilis the upper part of the spinal cord appears to 
be more involved than the lower part. In syphilitic leptomeningitis 
there are often extensive degenerations of the tracts in the cord. These 
involve particularly the lateral and posterior columns, giving rise to a 
combined sclerosis; and, in addition, there is often a narrow band of 
sclerotic tissue encircling the cord and lying immediately beneath the 
pia. 

Tumors of the pia are principally angiomata, endotheliomata, and 
fibromata; sarcoma and degenerative tumors like myxoma may occur. 
Neurofibroma, chiefly near the nerve-roots, is reported. Secondary 
tumors are carcinoma, sarcoma, and so-called myeloma. They produce 
symptoms like those noted under the dural tumors. 

ANATOMY OF THE CORD 

The spinal cord is composed, as are the other parts of the central nervous system, 
of gray and white matter, the gray matter occupying the central part and the 
white matter being distributed around it. The cord is of varying size, somewhat 
broader and flatter in the cervical region than elsewhere; almost circular in the dorsal 
region, and again thicker in the lumbar region. It communicates with the rest of the 
body by means of the spinal nerves, which arise anteriorly and posteriorly as roots. 
It is surrounded by three membranes: the pia, adherent to it; the arachnoid, adherent 
to the pia, but not dipping into the anterior fissure, and the dura mater, which is 
adherent neither to the arachnoid nor to the vertebral column. The gray matter 
is divided into two parts by the anterior commissure and posterior septum, each part 
consisting of an anterior horn, a thick, roundish mass, and a posterior horn, a slenderer 
projection. The lateral halves are united by the gray commissure, in which is the 
central canal lined with cuboidal epithelium and continuous with the fourth ventricle 
above. In the anterior cornua are found the large multipolar ganglion-cells, whose 
axis-cylinders pass out through the anterior roots and end in the muscles; commenc- 
ing in the dorsal region, there is a group of cells in the inner portion of the posterior 
horn, near the gray commissure, which are bipolar and whose axis-cylinders pass 
outward to the cerebellar tract, in which they ascend to the vermiform process of the 
cerebellum. The posterior roots are composed of fibers that originate in the spinal 
ganglia and pass into the cord. These spinal ganglion-cells have a single process, 
which appears to divide into two fibers, one passing outward into the peripheral nerves 
and usually terminating in the sensory corpuscles of the skin, the other passing inward 
through the posterior root to the spinal cord. The white substance of the spinal cord 
is composed of bundles of nerve-fibers that have, for the most part, a common 
function, a common mode of origin and of termination. 

Anatomically, the cord may be divided into three regions: anterior, lateral, and 
posterior, although these do not correspond to regions embryologically distinct. 
According to the manner of development, it should be separated into the anterolateral 
and the posterior regions. 



932 



A TEXT-BOOK OF PATHOLOGY 



The most important bundles of fibers in the anterolateral columns are those known 
as the pyramidal tracts, for the reason that they are continuations of the pyramids 
of the medulla. They originate in the motor region of the cerebral cortex and, in the 
first cervical segment, decussate through the representatives of the anterior cornua to 
reach their situation in the lateral columns. This decussation does not occur in all 
of the fibers, many passing down in the direct pyramidal columns and some without 
decussatipn in the lateral columns. These undecussated fibers subsequently cross 
to the other side through the anterior or white commissure. The fibers of the pyra- 
midal columns terminate in arborizations winch surround, but are not in contact 
with, the ganglion-cells of the anterior cornua. 

The cerebellar tract has already been described. Anterior to it and close to the 
periphery.of the cord is the so-called anterolateral column of Gowers. The fibers which 
form this probably originate in the lateral groups of cells in the anterior cornua and 
in the cells in the middle portion of the spinal cord. The column increases in size 
upward and degenerates in the same direction. Its termination is unknown. It 
also contains fibers that degenerate downward, of whose origin and termination we 
are ignorant. 

The rest of the anterolateral column is composed of short fibers, uniting different 
segments of the spinal cord. 

The posterior columns are composed of the fibers that enter by the posterior 
roots. These fibers divide into two branches, one ascending and the other descend- 
ing, the latter terminating in the gray matter of the posterior horn. The ascending 
fibers may be divided into two groups, the lateral and median bundles. The fibers 
of the lateral bundle are somewhat finer and evidently belong embryologically to a 
different period, because they acquire their myelin-sheaths later. They pass directly 
into the zone of Lissauer, and thence into the substantia gelatinosa of Rolando, 
and some of them terminate in arborizations about the ganglion-cells in the column 
of Clarke. The fibers of the median bundle are coarser. They pass inward, then 
upward along the inner side of the posterior horns, and then become the column of 
Bvrdach. The median fibers from the lower part of the cord bend inward and con- 
tinue their course in the column of Goll, terminating finally in the nucleus gracilis 
of the medulla oblongata. The fibers that enter the cord in the cervical region pass 
upward in Burdach's column and terminate in the nucleus cuneatus. Other fibers 
pass forward to the ganglion-cells of the anterior cornua, and have been supposed to 
be concerned in reflex action. Others decussate in the posterior commissure and 
then pass upward in the posterior columns of the opposite side. At somewhat regular 
intervals they give off at right angles fine collateral branches, which pass forward, 
and some of them, at any rate, end in arborizations about the cells of the anterior 
cornua of the gray matter. These are known as the reflex collaterals of Kolliker. 
A small portion of the posterior column just back of the gray commissure appears 
to be composed of fibers uniting the different segments. Physiologically, the spinal 
cord may be regarded as a series of superimposed centers which contain cells sending 
or receiving impulses to or from the periphery, and bands of fibers that unite these 
centers with the brain. The functions of these different tracts have already been 
discussed in the Anatomy of the Brain. An important function of the spinal cord is 
the accomplishment of reflexes. The centers for these reactions are situated in various 
portions, and according as these portions are intact or involved the reflexes persist 
or disappear. By means of the distribution of the sensory and motor disturbances 
and the alterations in the reflexes, accurate localization of a lesion in the cord is 
often possible. 

The lymph-channels of the cord are of some importance in inflammations by 
continuity. The conclusions of Bruce and Dawson upon their anatomy indicate 
that they follow the adventitia of the capillaries, veins, and arterioles toward the 
surface of the cord where they enter the deep layer of the pia, through which they 
probably communicate with the subarachnoid space. "The lymphatic path has 
in the main an outward direction, but there is no doubt that it permits of a current 
inward, or of an invasion by cellular elements, micro-organisms, and toxic substances." 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 933 



CONGENITAL ABNORMALITIES 

Total absence of the cord, or amyelia, only exists in associa- 
tion with anencephalus. It is interesting to note that the spinal ganglia 
usually persist. 

Abnormal smallness is known as micromyelia. The cord may 
be normal in structure, all the elements being proportionately reduced, 
but more commonly only certain parts are affected, particularly the 
pyramidal columns, as a result of fetal lesions in the motor tract. 

Double cord, or diastematomyelia, is usually localized to one 
portion of the cord, particularly the lumbar region. Occasionally the 
cord is completely divided by a bony septum. In this case the gray 
matter in either half presents the normal arrangement of the gray 
matter in the cord. 

Unusual length of the cord may also occur, the conus terminalis being in these 
cases elongated and extending to the end of the sacrum. The spinal roots may be 
excessive or defective in number on one or both sides. This usually occurs in the 
dorsal region, the commonest condition being the presence of eleven roots on one side. 
The cord may be asymmetrical. This usually involves only the pyramidal columns, 
and is due to incomplete decussation. 

Heterotopia of the gray matter is not infrequent. This may con- 
sist of doubling of one of the horns, abnormal relation of gray and white 
matter, disorganization of one or both horns, or fissures extending into 
the substance. According to van Giessen, the majority, if not all, of 
these cases are the result of injury during removal, and are therefore 
to be regarded as artefacts. This statement is, however, too sweeping. 
Abnormal bundles, producing heterotopia? and due to alterations in the 
medulla or even higher in the central nervous system, have been found. 
These appearances may also be produced by tumors or other conditions 
causing pressure. 

Dilatation of the Central Canal. — The central canal may be 
dilated, either locally or throughout its whole length. This condition 
is known as hydromyelia, or hydrorrhachus, and is akin to hydrocephalus, 
with which it is sometimes associated. Hemorrhage may take place 
into these dilated canals and gives rise to hematomyelia (vide infra). 

Localized collections of liquid in the subarachnoid spaces are some- 
times spoken of as hydrorrhachus externa. 

Spina Bifida. — There may be imperfect closure of the posterior 
processes of the vertebrae, giving rise to clefts, which are known as 
rachischisis. If the membranes of the spinal cord protrude through 
the cleft in an imperfectly closed canal in the form of a sac or hernia, 
the condition is called spina bifida. In some cases the skin is still 
present, and is often covered by an abnormally thick growth of hair. 
In other cases the pia is the only membrane that enters into the forma- 
tion of the wall. It is usually thickened, and may be covered with 
granulations. The spinal cord may be incompletely or normally formed 
and hang in the sac. Sometimes the dilatation evidently takes place 



934 



A TEXT-BOOK OF PATHOLOGY 



in the central canal, for the substance of the spinal cord may be recog- 
nized adhering to the inner layer of the pia mater. This condition is 
called myelomeningocele. Spina? bifida? usually appear in the sacral or 
lower lumbar region, although rachischisis may involve the entire length 
of the vertebral canal. 

Rarely a cystic dilatation of the meninges may take place between 
completely formed vertebral arches. 



Hydromyelia is a condition in which the central canal of the 
spinal cord is dilated. It frequently occurs in circumscribed portions 
and is apparently without clinical significance. More rarely the whole 
canal has a macroscopical lumen throughout its entire length, particu- 
larly in cases of hydrocephalus, although in the majority of cases of 
this latter disease the spinal cord is not involved. A patulous canal 
can be distinguished from a pathological cavity by the fact that the 
canal is lined by the normal cuboidal epithelium of the ependyma. 
Usually there is a considerable collection of ependymal cells in the 
neighborhood of the central canal, and this is more apt to be the case 
if it is dilated or otherwise altered than if it is normal. Occasionally 



the central canal is doubled. This rarely happens throughout the 
whole length of the cord, but is more frequently found in a limited por- 
tion, especially the lumbar region. This doubling is due in some in- 
stances to the obliteration of the central part of a dilated canal with 
its long axis transversely placed. Sometimes a slit-like canal shows a 
dilatation in only one part. At places the lumen of the canal may be 
completely obliterated, leaving nothing but a mass of cells in the gray 
commissure, in the midst of which capillaries may be observed. More 
distinct pathological changes are diverticula that occasionally spring 
from the canal. These seem to be most frequent in the cervical and 



HYDROMYELIA AND SYRINGOMYELIA 




Fig. 432. — Hydromyelia (partly diagrammatic). 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 935 

dorsal regions. They usually extend downward, and are situated poste- 
riorly to the gray commissure. It is possible that collections of epi- 
thelial cells from the ependyma under similar circumstances may form 
masses in the posterior column without distinct cavity formation, 
although this is doubtful. These changes are particularly significant 
on account of their relation to the disease known as syringomyelia 
(Fig. 432). 

Syringomyelia. — Pathologically, this is essentially a cavity in the 
spinal cord that is not lined throughout with the columnar epithelium 
of the ependyma. This cavity may appear as a wide dilatation or as a 
narrow slit. It usually occupies the posterior part of the cord, is exceed- 
ingly asymmetrical, sometimes limited entirely to one side, and in these 
cases is ordinarily found in the posterior horn or on its inner side. The 
cord may be unaltered externally. The dura mater is commonly normal. 
The pia and arachnoid are either normal or else thickened slightly, the 
change being not unlike that found in senility or in cases of chronic 
edema of the membranes. The shape of the cord may be entirely 
normal. This, however, is rare. Usually there is some asymmetry, 
and frequently, particularly if the cavity be large, the cord upon being 
removed and laid upon a flat surface seems to collapse, giving rise to 
the so-called ribbon appearance. Section through the cord shows the 
existence of a larger or smaller cavity filled with the products of lique- 
faction-necrosis, cerebrospinal fluid, or more rarely with blood. Some- 
times it appears to have been empty, in which case the cord prob- 
ably was collapsed in the spinal canal and the space thus formed was 
filled with cerebrospinal fluid. The solid portion of the cord is usually 
somewhat darker in color, and the distortion of the outline corresponds 
to the extent of the process. The portions of spinal cord not involved 
by the lesion, and below it, commonly show more or less descending 
degeneration. In the portion above the cavity, if it does not extend 
as far as the medulla, some degeneration in the posterior columns is 
often found. In many cases, however, both the ascending and descend- 
ing tracts are intact; at least they appear so to the naked eye. Micro- 
scopical examination shows that the cavity is bounded, as a rule, by a 
delicate reticulum of hyperplastic neuroglia. Sometimes this is lined 
with what appears to be connective tissue, and is supposed to be an inclu- 
sion of the pia mater; at other times it is lined with ependymal epithe- 
lium. The tissue in the neighborhood is usually hyperplastic neu- 
roglia. The cord in the immediate neighborhood may show curiously 
few changes, the ganglion-cells being perfectly normal and the fibers 
uninjured. If the cavity is extensive and the proliferation of the neu- 
roglia considerable, this is not the case. An entire posterior root may 
be destroyed, or perhaps half or more of the spinal cord will be exten- 
sively degenerated; in these cases secondary degeneration always occurs. 
Not only the pyramidal tracts, but also bundles in the posterior columns 
degenerate downward. In a case that was studied by one of us the 
comma tract of Schultze was beautifully outlined. The nerve-roots are 
also usually involved, and there is descending degeneration along the 



936 



A TEXT-BOOK OF PATHOLOGY 



anterior roots, which may be detected also in the nerves. The poste- 
rior roots may show some degeneration, but this is rare and the cells of 
the spinal ganglia are usually intact. Sometimes there is considerable 
vascular proliferation in these portions of the cords not unlike cavernous 
change. There is at times so active a gliosis that a suspicion of glioma- 
tous or sarcomatous change has arisen ; the seat of this change is char- 
acteristically in the tissue in the vicinity of the central canal. 

As syringomyelia is particularly a disease of the central portion 
of the spinal cord, the fibers that convey pain and temperature sense 
are essentially involved, and, as a result, one of the characteristic 
changes is the dissociation of sensation — that is to say, persistence . of 
tactile sensation with thermo-anesthesia and analgesia. In addition, 
as the cells of the anterior cornua are involved, there is degeneration 
in the muscles that they supply. 

The most widely accepted theory for the origin of this condition is that the process 
is one of gliosis arising from the ependyma of the central canal, since glia tissue is in 
all probability the descendent of ependyma. This proliferation of the ependyma 
and metaplasia to glia tissue is assisted by congenital malformation and vascular 
conditions of congenital or inflammatory nature. The softening proceeds within 
the areas of glia proliferation by pressure and lowered nutrition. Conditions favor- 
ing hydromyelia will, therefore, predispose to syringomyelia. 

CIRCULATORY DISTURBANCES 

Diseases of the walls of the blood-vessels are similar to those 
occurring in the blood-vessels of the other parts of the body. Exten- 
sive atheromatous changes are relatively rare. Perhaps the most fre- 
quent disease is hyaline degeneration, which is exceedingly common in 
cases of sclerosis, and may occur in early life, even in childhood. It is 
almost invariably present in the cords of persons dying after middle life. 
Round-cell infiltration of the intima {endarteritis) occurs in syphilis, 
and also, though less frequently, in tuberculosis. Fibrous thickening 
of the intima and proliferation of the connective tissue of the adven- 
titia are common senile changes. 

Attention has been directed more particularly to these changes 
on account of the suggestion by Redlich that they are the anatom- 
ical basis of paralysis agitans. According to him, the character- 
istic changes are endarteritis and periarteritis, with extension of the 
latter process into the surrounding nerve substance and the formation 
of perivascular insular scleroses. In addition, there is often some 
degeneration in the posterior columns, and occasionally in the lateral 
columns in the cervical and lumbar enlargements. The vascular 
changes, curiously enough, appear to be more severe in the posterior 
horns than in the other parts of the cord, and amyloid bodies are nearly 
always present in these regions. However, in examining the cord of a 
typical case of paralysis agitans one of us failed to find these lesions, 
while in another case, equally characteristic clinically, they were quite 
pronounced. More information is to be desired upon this disease. 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 937 



Miliary aneurysms are very infrequent in the spinal cord. Aneur- 
ysms of the vertebral arteries, however, sometimes involving the com- 
mencement of the spinal branches, have been reported, but are rare. 

Active hyperemia of the spinal cord is rather a clinical hypothesis 
than a pathological entity. Occasionally, however, the gray matter 
seems to be slightly darker than normal, and there is rather free bleeding 
from the vessels cut transversely. In many cases of myelitis the arteries 
and capillaries may be found distended with blood. 

Passive hyperemia is more readily detected in the veins of the 
membranes than in the cord itself. 

Anemia is an important and easily recognized condition. Experi- 
mentally, it has frequently been produced by ligation of the abdominal 
aorta. Cases have occasionally occurred in human beings in which 
this vessel was occluded by a thrombus, giving rise to similar changes. 
The cord, under these circumstances, is somewhat swollen, pale, and 
soft; not invariably, however, for cases have been reported in which 
microscopically it was entirely normal. The ganglion-cells, particularly 
those of the anterior cornua, are most distinctly affected. They exhibit 
usually the characteristic features of chromolytic degeneration. Similar 
changes may occur in other portions of the cord, but are exceedingly 
rare, partly on account of the free anastomosis of the blood-vessels, 
partly because if, as sometimes happens, thrombi are formed in the 
vertebral arteries, death occurs before characteristic changes have had 
time to develop. 

Varicose Veins. — Occasionally a group of vessels in one part of 
the spinal cord will be dilated and varicose, forming a sort of plexiform 
angioma. Angiomatous formations are frequently observed in various 
forms of myelitis and sclerosis. 

Hemorrhages may be of two kinds: jmnetate and massive. 

Punctate hemorrhages are really nothing but pericapillary exudations 
of blood-cells, which can readily be distinguished from the drops of 
blood that form at the cross-section of blood-vessels by the fact that 
they cannot be washed off. It is probable that if death does not occur 
at once they are in great part absorbed, leaving perhaps a minute scar 
that may be readily overlooked. These minute hemorrhages are per- 
haps more common in the cervical region than elsewhere. They are 
found in the course of infectious diseases, particularly those affecting 
chiefly the nervous system, such as tetanus, and especially hydrophobia. 
Small agonal hemorrhages into the substance of the spinal cord, particu- 
larly in the region of the central canal, are not uncommon. Occa- 
sionally these may be visible to the naked eye; they are, of course, to 
be distinguished from antemortem changes by the regular form of the 
blood-cells and the absence of blood-pigment. They are only impor- 
tant on account of the possibility of their being mistaken for patho- 
logical changes. 

Massive hemorrhages may be infiltrating or circumscribed. In the 
former the blood is found between the nerve-fibers and in the meshes 
of the neuroglia. The nerve substance is usually more or less degener- 



938 



A TEXT-BOOK OF PATHOLOGY 



ated, and the lesion corresponds anatomically to the hemorrhagic infarct. 
Circumscribed hemorrhages are usually small when compared to those 
in the brain, a circumstance due, of course, to the restricted area in 
which they can occur. 

They do damage, of course, at once, by the separation of the fibers 
and cells; the greater damage, however, results from the pressure of the 
clot within the closely attached meninges. If the meninges be opened, 
thus relieving the tension, degeneration is much less apt to occur. 

The most common cause of this form of hemorrhage is traumatism, 
and it may sometimes occur as a result of concussion without fracture 
of the spinal column. Hemorrhages may also occur in persons with 
diseased arteries as a result of violent effort or emotional disturbance. 

The clots are usually irregularly oval in outline, and are often sur- 
rounded by hyperplastic neuroglia, in the midst of which are found 
compound granular cells, and more or less degenerated nervous tissue. 

In the later stages the formation of fibrous tissue is apparent; capil- 
laries may also be found bending into the substance of the clot, which 
eventually is absorbed, leaving a scar that nearly always contains some 
pigment surrounded by coarse-meshed neuroglia tissue. Rarely the 
pigment is absorbed and a cyst remains. Occasionally the hemorrhagic 
focus is restricted to the gray substance, the blood being found in cylin- 
drical masses. This arrangement is due to the fact that in normal cir- 
cumstances the gray matter is softer than the white, and offers less 
resistance to the extravasation of the blood. In this case the infiltrated 
area soon becomes filled with granular cells, the nerve-fibers degenerate, 
and crystals of hematoidin appear. 

Hematomyelia. — If the central canal is dilated and contains blood, 
the condition is known as hematomyelia. This may occur as the result 
of traumatism or because of some vascular degeneration. The latter 
form is occasionally associated with syringomyelia, and is found most 
frequently in the cervical portion of the cord. If the hemorrhage 
occurred some time before death, the only traces that persist will be 
discoloration of the ependyma, and perhaps the adjacent tissue. Hemor- 
rhage may also occur during the death agony, in which case the central 
canal may either be filled with normal blood-cells, or, if it is at all 
dilated, there will be a thin layer of blood-cells upon the surface. The 
most common situation is at the point where the central canal opens into 
the fourth ventricle. 

INFLAMMATION 

Myelitis, in the strict sense, is a term signifying an inflammation 
of the substance of the spinal cord. According to this view, it should 
be limited exclusively to forms of spinal disease secondary to hemato- 
genous infection, extension from the pia, or possibly extension from the 
central canal, although the latter can be dismissed as an unknown 
variety. The name has been used, however, to signify any form of 
softening that may occur, whether it be produced by injury or disease 
of the spinal column, by tumors, or by poisons circulating in the blood. 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 



939 



It has also been applied to secondary changes the result of meningitis 
and to obscure lesions that either commence with a proliferation of the 
neuroglia, or as a primary degeneration or atrophy of the nerve sub- 
stance and secondary increase in the neuroglia tissue. According to the 
distribution of the lesions, myelitis is spoken of as circumscribed, trans- 
verse, or disseminated. 

Hematogenous Purulent Myelitis. — As a rule, the membranes of 
the brain are also infected, and show the characteristic appearances of 
acute leptomeningitis, with subarachnoid accumulations of pus and 
injection of the vessels. Cross-section of the cord shows here and there 
small reddish or yellowish areas distributed irregularly throughout the 
cord; in longitudinal sections these usually appear as streaks following 
the course of the blood-vessels. The cord often seems to be softer and 
may be darker than normal. The microscopical changes consist of 
accumulations of pus in the pia mater and distention of the vessels, the 
presence of a perivascular round-cell infiltration, slight degeneration 
of the nervous tissue in the neighborhood of the lesions, and alteration 
of the neuroglia, which may show some looseness of its fibers. Altera- 
tions may be seen in the ganglion-cells, which consist chiefly of irregular- 
ity in the arrangement of the chromophilic bodies and perhaps some- 
what diffuse staining. Should, however, ganglion-cells lie in the midst 
of, or very close to, the purulent focus, they show a severer type of 
degeneration and often lose their protoplasmic processes. In these 
cases micro-organisms are not infrequently found. 

Myelitis secondary to purulent leptomeningitis is not greatly dis- 
similar from this, excepting that there is generally a more marked degen- 
eration in the periphery of the cord. The neuroglia cells are increased 
in this region; there are often minute hemorrhagic foci, and occa- 
sionally small peripheral accumulations of pus. These lesions have 
been observed, particularly by Councilmann, in epidemic cerebrospinal 
meningitis. 

Transverse myelitis, without local foci, secondary to injury or infec- 
tious disease — that is, the condition generally denominated myelitis — 
presents three stages — the stage of red softening, of yellow softening, and 
of gray degeneration. In the first the membranes of the cord are usually 
somewhat opaque. The substance of the cord itself may be either 
swollen or shrunken, and is softer than normal in consistency. Upon 
section of the cord the surface is seen to be pink, and there may be 
minute hemorrhages; the tissue swells so that the surface of the cross- 
section is slightly convex. Microscopically, the most characteristic 
feature is the congestion of the blood-vessels ; this is more marked in the 
veins than in the arteries. There is usually a considerable amount of 
perivascular cellular exudate, the majority of these cells being poly- 
nuclear leukocytes. The myelin-sheaths show here and there degen- 
eration; the axis-cylinders are swollen, granular, and somewhat shrunken. 
The neuroglia cells are sometimes swollen, sometimes irregular in out- 
line and increased in number. The neuroglia fibers in the neighborhood 
of the vessels form a loose, irregular network. The ganglion-cells show 



940 



A TEXT-BOOK OF PATHOLOGY 



pronounced alterations, usually similar to those already described as 
occurring in intoxication, such as irregularity in staining, peripheral 
situation of the nucleus, and varicosity or fragmentation of the proto- 
plasmic processes. If the process has lasted any considerable time, the 
most characteristic feature of myelitis, namely, the accumulations of 
granular cells, begins to take place. It is not certain what these cells 
are, but in all probability they represent the wandering connective- 
tissue corpuscles that have absorbed the granular fatty detritus of the 
myelin fibers. Occasionally, hyaloid bodies are present, even in con- 
siderable numbers. These are more irregular in outline than those seen 
in more chronic conditions, and, according to Leyden and Goldscheider, 
are probably due to coagulation of an inflammatory exudate. In the 
next stage a pressure-anemia begins to be apparent. A cross-section 
through the freshly removed cord shows that it is still somewhat swollen ; 
the color is yellow. The distinction between the gray and the white 
matter is preserved, but the gray matter is distinctly shrunken. Micro- 
scopically, the blood-vessels are shrunken; the perivascular cellular 
exudate is still present, but many of the cells contain fat-droplets. 
Throughout the whole cord are found compound granular cells, giving 
to it a peculiar and characteristic appearance. The nerve-fibers are 
swollen, granular, or shrunken. The myelin-sheaths are filled with 
droplets of fat, or have partially disappeared. The neuroglia may be 
still looser in its texture. The neuroglia cells are more apt to show de- 
generative changes. In this stage the alterations in the ganglion-cells 
are extreme. They may be swollen and irregular; often they form 
irregular, vacuolar-looking masses; some, however, are shrunken, stain 
dark, and exhibit no trace of a nucleus. Others may perhaps be still 
recognized by the presence of a small vesicle containing the peculiar 
brownish pigment, and finally it is evident that some have wholly disap- 
peared, because the number is much less than normal. In the severest 
grades of this condition the substance of the cord has undergone lique- 
faction and is reduced to a puriform mass, which it is impossible to 
examine, excepting upon films. It is then found to contain fat-droplets, 
granular cells, and detritus. In the stage of gray degeneration there is 
a secondary distention of the blood-vessels, giving it a somewhat redder 
appearance. There is proliferation of the connective tissue, which has 
a tendency to retract and cause concavity of the surface of the section. 
The granular cells are found chiefly in the neighborhood of the blood- 
vessels. The neuroglia tissue is looser and appears to enclose numerous 
vacuoles. The nerve-fibers have in large part disappeared, although a 
few show degenerative changes, and the ganglion-cells are reduced to a 
few masses of pigment or else have disappeared entirely. After the 
cord has hardened, as occurs sometimes in various forms of sclerosis, 
cracks may appear in its substance from the retraction of the connective 
tissue. By this time secondary degenerations usually begin to appear 
above and below the lesion, particularly in the sections stained by 
Marchi's method. 

Pressure-myelitis. — The alterations produced in the cord by slowly 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 941 



developing pressure, such as the growth of a tumor in the membranes, 
or gradual bending of the spinal canal, as in Pott's disease, produce 
somewhat characteristic changes. The cord at first becomes anemic, 
due to the mechanical occlusion of blood-vessels in the affected seg- 
ment. As the pressure increases and the anemia continues degenerations 
ensue in the white matter. These are accompanied by the appearance 
of a moderate number of granular cells and by slight proliferation of 
the neuroglia. It appears that this degeneration affects first the myelin- 
sheaths, and that the axis-cylinders may maintain their vitality for a 
considerable length of time, for regeneration has occurred after the 
cord has been considerably reduced in size by long-continued pressure. 
The gray matter appears to persist for a longer time. This does not 
mean that the ganglion-cells remain absolutely intact, for in the early 
stages of the process they exhibit various degenerative changes. As we 
already know, however, such degenerative changes are not necessarily 
fatal to the vitality of the cell. Later, they begin to shrink, usually 
becoming at first darker, then losing their protoplasmic processes, and 
ultimately undergoing change into small irregular vesicles that are 
frequently pigmented. The neuroglia gradually proliferates, and 
ultimately the cord is converted into a sclerotic mass at the point of 
pressure. This mass is gray in color, seems dry, and often in the process 
of hardening develops numerous irregular fissures. The central canal 
is variously affected. It may be, at different levels, obliterated, dilated, 
doubled, or even tripled. This appearance of doubling or trippling, 
however, is due to the extrusion of diverticula, which pass upward or 
downward more or less parallel to the axis of the cord. The epithelium 
lining the central canal maintains its vitality to a remarkable degree, 
and, even when all other nervous structures have disappeared, stains 
distinctly, and is of normal shape. Frequently the endothelium lining 
the under surface of the pia, or the lymph-channels arising from it, 
proliferate to a remarkable degree, and large masses of endothelial cells 
may be found either immediately beneath the pia or more deeply situ- 
ated in the substance of the cord. In some cases this appears to be 
almost a tumor formation. Secondary degenerations, of course, occur 
as soon as the axis-cylinders begin to swell, and are identical with those 
found in other complete transverse lesions. 

Acute Anterior Poliomyelitis. — In this disease, clinically desig- 
nated infantile palsy, the ganglion-cells of the anterior cornua of the 
spinal cord, their neuraxons passing out through the anterior roots, 
and the muscles over which they have trophic influence, are the princi- 
pal parts involved. The disease is undoubtedly due to hematogenous 
intoxication or infection. It develops after exposure to cold, subse- 
quent to some other infectious disease, such as scarlet fever or measles, 
and occasionally has appeared as an epidemic. Children are almost 
exclusively affected, usually about the period of the second dentition, 
except in the epidemic form, when any age is liable to an attack. The 
nature of the poison that causes it is unknown. (See chapter on Filter- 
able Viruses.) 



942 



A TEXT-BOOK OF PATHOLOGY 



Macroscopically the cord presents no characteristic external altera- 
tions. If section is made through the diseased portion, it can be seen 
that the tissues of the cord are somewhat redder than normal, particu- 
larly the anterior cornua of the gray matter, and minute hemorrhages 
may also be observed in this region. The tissue is somewhat softer 
than normal, and the blood-vessels are considerably distended. In 
old cases — that is, those with changes consecutive to the cessation of 
the acute process — the cord may be smaller and somewhat denser. 
Upon section it is readily observed that one or both of the anterior 
cornua are considerably reduced in size. The anterior roots from the 
diseased area may be considerably shrunken and fibrous. Microscopic- 
ally, in the early stages the most striking appearance is that presented 
by the blood-vessels. These are greatly distended and surrounded by a 
wall of round cells. The vessels in the gray matter of the anterior 
cornua, in the anterior commissure, and in the anterior septum appear 
to be chiefly involved. The posterior half of the cord presents few, if 
any, alterations. The neurogliar tissue seems to be somewhat looser, 
and throughout all the affected tissue there is more or less mononuclear 
cellular infiltration. The ganglion-cells are much altered. They may 
be swollen and colorless, the chromatin granules may be arranged in 
irregular masses, the processes are irregular, the nucleus may stain 
diffusely, and the nucleolus show vacuolar degeneration ; the pericellular 
space is either distended by edema or by mononuclear cells. In all 
cases there seems to be a primary round-cell infiltration of the pia 
mater, which also penetrates the cord and follows the connective tissue. 
In the more advanced stages both nucleus and protoplasmic processes 
have disappeared, leaving nothing but the thickened axis-cylinder spring- 
ing from the cell. The perivascular spaces may be somewhat distended, 
and often contain round cells. Even in cases examined a few days after 
the onset it is evident that some of the ganglion-cells have degenerated 
completely and have disappeared, as their number is markedly dimin- 
ished. The fibers of the anterior roots show the ordinary forms of 
degeneration, the presence of globules of fat in the sheaths, and swelling 
or fragmentation of the axis-cylinders. The affected muscles very early 
exhibit fatty degeneration and atrophy of the fibers. In cases examined 
several months after onset considerable atrophy has usually taken place 
in the anterior horns. The perivascular round-cell infiltration is still 
very distinct, and usually compound granular cells are found in consider- 
able numbers in the lesions. The ganglion-cells are fewer, and those 
that remain may be either normal or partially degenerated. Many 
fibers have disappeared from the anterior roots, and the trophic changes 
in the muscles are still more pronounced. In those cases examined very 
late — that is, some years after the development of the process — the 
anterior horns appear to be markedly diminished in size, although this 
alteration is exceedingly unequal, often one horn being involved whilst 
the other is perfectly normal or exhibits only slight alterations. Occa- 
sionally the anterior horns appear paler, but of almost normal size, 
apparently the result of a colloid degeneration of the neuroglia tissues. 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 943 

The blood-vessels are dilated and their walls thickened, and they may 
contain some cellular infiltration. In those parts where the process is 
most severe all the ganglion-cells have disappeared; in others a few 
may remain, and these are usually normal. The neuroglia has under- 
gone hyperplasia, and consists of a coarse meshwork containing many 
nuclei. The medullated fibers of the anterior roots are partially or 
completely destroyed. Degeneration of the medullated fibers of the 
pyramidal tract may sometimes be traced for a few segments above the 
affected region; as a rule, it is slight, and involves only a few of the 
fibers. The lesions usually attack several segments of the cord, and are 
most frequent in the lumbar region, although any part may be affected, 
even the cells of the medulla. 

The pathogenesis of the disease cannot be said to be settled, but it 
seems that virus arrives in the spinal cord by way of the anterior 
spinal artery and its accompanying lymph-channels. Within the cord 
it seems probable that spread occurs along the lymphatics. 

The clinical course of the disease is sufficient evidence of the fact 
that at least some of the cells recover their functions completely. After 
the paralysis has reached its greatest extent a very considerable degree 
of recovery may ensue, and only certain groups of muscles remain 
affected. Some of these degenerate and contract, giving rise to various 
deformities in the limbs. 

Landry's ascending paralysis is an acute spreading general muscular 
palsy due usually to an ascending myelitis, alone or combined with 
degenerative peripheral neuritis. The histological change in the cord 
may be that of poliomyelitis or a total ascending myelitis. The disease 
appears as a sequel to some of the acute infections, such as enteric fever, 
or without apparent antecedent cause; for such attacks many bacteria 
have been held responsible, but the cause is not yet settled. During 
an epidemic of poliomyelitis it is common to meet ascending and ful- 
minating cases of the Landry type. 

Inflammation of this class, that is, chiefly affecting the motor cells, 
may either ascend to or primarily involve the bulb or basal ganglia and 
cause superior poliomyelitis or polio-encephalitis. Pathologically the 
changes are the same, but there is relatively less tendency to gross 
degenerations. The lesions affect, of course, the ganglia of the cranial 
nerves. (See Bulbar Palsy.) 

Tuberculosis, aside from tuberculous meningomyelitis, is rare, but 
may occur as miliary tubercles or by coalescing of these into larger gran- 
ulomata. They cause transverse myelitis. Syphilis of the cord is said 
to appear as an acute degenerative myelitis in the secondary stage, and 
may occur as secondary to luetic meningitis. The most important 
results of syphilis are the fibratic and degenerative lesions like tabes. 

PRIMARY DEGENERATIONS OF THE CORD 

Primary degeneration of the spinal cord is characterized by the more 
or less complete destruction of certain systems of fibers, affecting their 



944 



A TEXT-BOOK OF PATHOLOGY 



whole length, without solution of continuity in any part of their course 
or distinct degenerative changes in the ganglion-cells from which they 
arise. Certain groups of fibers appear to be more frequently affected 
than others ; these are particularly the columns concerned in the conduc- 
tion of impulses from or to the brain. They may be classified as follows: 
(1) The sensory neurons of the cord, which are composed of the unipolar 
cells of the spinal ganglia, and their neuraxons. They pass from the 
posterior roots into the spinal cord, and enter first the column of Burdach, 
subsequently bending into the column of Goll, and ending in the nuclei 
of Goll and Burdach in the medulla. (2) The central motor neurons, 
commencing in the pyramidal layer of the motor cortex, passing down 
through the internal capsule, the pyramids, and the pyramidal columns 
of the cord. (3) The peripheral motor neurons, commencing in the 
ganglion-cells of the anterior cornua, passing out from the anterior 
groups, and terminating in the muscles. 

The most important primary degeneration is tabes dorsalis, or 
posterior sclerosis; it involves almost exclusively the sensory neuron. 
Involvement of the peripheral motor neuron gives rise to the disease 
known as progressive spinal muscular atrophy; degeneration of both 
motor neurons, to amyotrophic lateral sclerosis. 

Posterior Sclerosis 

Degeneration of the posterior columns, when occurring independ- 
ently of distinct lesions of the posterior roots or section of the spinal 
cord — that is, as a definite form of disease — is known as tabes dorsalis, 
and corresponds clinically to locomotor ataxia. 

There has been considerable discussion of late years as to whether this is due to 
systemic disease attacking primarily certain columns or tracts of fibers in the spinal 
cord, or to a condition secondary to disease of the posterior roots. 

Trepinski has combated the latter view, as a result of the comparison of the areas 
of degeneration in certain cases of locomotor ataxia with the areas of myelination in 
the cords of human fetuses. He believes that tabes is strictly a systemic disease, 
and Schaffer partially agrees with him. Obersteiner, however, after a careful 
review of their work, still adheres to the theory that the posterior roots are primarily 
affected. 

The fibers of the posterior roots appear to originate in the spinal ganglia. Upon 
entering the cord they divide into the ascending and descending branches, both of 
which give off collaterals. They may be divided into two groups, the lateral and the 
median bundles. The lateral fibers are somewhat finer and evidently belong embry- 
ologically to a different group, because they acquire their myelin-sheaths later and 
pass directly into the zone of Lissauer, thence into the substantia gelatinosa of 
Rolando, and some of them terminate in arborization about the cells of the columns 
of Clarke. The median bundles, which consist of coarser fibers, pass inward, then 
upward to the inner side of the posterior roots, then bend in and form the columns 
of Burdach, and, finally, those from the lower regions of the cord enter the columns 
of Goll and terminate in the nucleus and the medulla. Experimental degeneration 
caused by section of the posterior roots in animals, or destruction of the posterior 
roots as a result of pathological processes in human beings, causes ascending degen- 
eration of the posterior columns that corresponds very closely in many respects 
to the lesions of tabes dorsalis (Fig. 433). 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 945 



Etiology. — It now seems to be well established that syphilis occurs 
more frequently in the previous history of cases of tabes and of general 
paresis than in the previous history of other forms of nervous disease. 
According to various sets of statistics, it varies from 50 to 90 per cent, 
in all cases (Erb). The theory that syphilis is the important factor in 
the causation of tabes has received considerable support from the find- 
ings of Xoguchi. This observer was able to detect the Spiroehoeta pallida 
in the cord of 12 out of 40 cases of tabes. The Wassermann reaction 
is positive in a large majority of instances. Nevertheless, a certain 
number of cases of tabes occur in persons who give no history of syph- 
ilis, have never had any symptoms of the disease, and present no signs 
of it at the time of examination. 

Various theories have been suggested to account for the special 
involvement of the posterior columns. Edinger has suggested that 
those portions of the central nervous system that are subjected to 




Fig. 433. — Sclerosis of the cord, from a specimen stained by Weigert's method. In the 
dark area the normal (unaffected) nerve-fibers are deeply stained. 

excessive work are more likely than the others to feel the action of 
any toxin that may exist in the body — such, for example, as the toxin 
of syphilis. Siebert has slightly modified this theory, suggesting that 
at the point where the posterior roots enter the spinal cord they are 
most likely to be subjected to injurious overgrowth of the neuroglia 
that may be produced by the presence of toxins, exposure to cold, 
etc. Hitzig believes that toxins may exist in the body for long periods 
of time, and so alter the blood as to cause it to produce in the more 
susceptible portions of the nervous system sclerotic changes. Ober- 
steiner has suggested that in all probability tabes is due to a va- 
riety of conditions, although he admits that syphilis is by far the 
most important. As far as we have been able to ascertain, only a 
single case has been recorded in which injury appears to have been 
solely responsible for the development of the disease. 

Pathological Anatomy. — The macroscopical lesions are as follows: 
The dura shows no changes; the pia mater in the segment between the 

60 



946 



A TEXT-BOOK OF PATHOLOGY 



posterior roots is somewhat thickened and opaque, a change which 
cannot usually be observed in the lateral and anterior regions. The 
posterior roots may be enlarged. In the advanced cases, however, they 
seem to be somewhat thinner and more translucent. On section 
through the cord the gray matter, especially that of the septum and 
anterior horns, appears to be normal. The anterior and lateral regions 
of the white matter are similarly intact. In the most advanced cases 
the white matter between the posterior roots is darker than normal 
and seems to be shrunken. Its consistency is somewhat softer than 
that of the normal cord, and the fact that it becomes depressed after 
section shows that there is some tendency to retraction. In early cases 
these changes may be slight; in fact, in cords removed from patients 
suffering from general paresis, in which the earliest stages are usually 
observed, there may be no macroscopical changes found. In these 
early stages sections stained by some myelin method exhibit the follow- 
ing changes: In the lumbar region the columns of Goll are degenerated, 
excepting the anterior portion; in the dorsal region there are usually 
two areas of degeneration in the column of Burdach; in the cervical 
region a portion of Goll's column is involved, and there are usually 
two areas on either side in the column of Burdach near the posterior 
horns. In nearly all cases there is usually more or less degeneration of 
the posterior roots. In the more advanced cases the portion of the 
posterior columns immediately behind the posterior commissure con- 
tains normal fibers, but all the rest of the posterior column and Lis- 
sauer's zone are degenerated. In the cervical portion the degenera- 
tion of the column of Goll is most pronounced, and there is only a small 
number of normal fibers anteriorly and on either side lying close to the 
posterior roots. The degeneration extends upward through the medulla 
as far as the nuclei of Goll and Burdach. It occasionally happens that 
one portion of the cord seems to be more severely affected than the 
others; as a general rule, this is the lumbar region or the dorsal and 
lumbar regions, whilst the cervical portion shows fewer changes. Occa- 
sionally, however, the cervical portion of the cord will be particularly 
involved and the other regions more or less intact. In these cases the 
columns of Goll show only slight degeneration, whilst in the cervical 
portion the column of Burdach is markedly degenerated. As the fibers 
turn toward the center healthy fibers from the posterior roots of the 
cervical segments are usually less involved, so that the degenerated 
area lies near the posterior median septum, in the region usually called 
the middle root-zone. These degenerated areas are characterized by 
destruction of the myelin-sheaths and the axis-cylinders, their places 
being taken by proliferated neuroglia, which is characterized by the 
appearance of thicker and somewhat wavy fibers. In the late stages 
this hyperplastic neuroglia may undergo considerable contraction 
(Fig. 434). Proliferation of the neuroglia cells may be observed in the 
earlier stages, but in the later stages this has largely disappeared. The 
degeneration of the fibers is in all respects similar to that of the ordinary 
secondary degeneration. Accumulation of the peculiar amyloid bodies 



DISEASES OF THE SPINAL COED AND ITS MEMBRANES 947 



is usually observed. The gray matter of the cord is little affected, the 
cells in particular rarely showing distinct traces of degeneration. The 
fibers that normally pass through the gray matter often disappear com- 
pletely. This is true especially of the fine fibers of Lissauer's zone and 
those that form the plexus around the cells of the column of Clarke. 
The reflex collaterals also frequently disappear, and this is supposed to 
explain the loss of the reflexes, which is a common symptom of the dis- 
ease. The vessels usually exhibit some thickening of the adventitia. 
and occasionally an accumulation of granular cells either in the adven- 
titia or beneath the ependyma. Hyaline degeneration is found occa- 
sionally. The pia mater, corresponding to its macroscopical appear- 
ance, shows some thickening of the fibers, although this is absent in the 
earlier cases. 

The most interesting subject connected with this disease is the con- 
dition of the peripheral nerves, the spinal ganglia, and the posterior 




Fig. 434. — Sclerotic and contracted posterior columns in posterior sclerosis (Karg and 

Schmorl). 

roots. Degeneration of the peripheral cutaneous nerves is frequently 
observed, the changes consisting of thickening of the perineurium and 
the connective-tissue trabecular, more or less degeneration of the myelin- 
sheaths, and occasionally swelling of the axis-cylinders. 

The results of the examination of the spinal ganglia have been 
very contradictory, and some authors find them intact, while others 
describe contraction and irregularity in the outlines of the cells. In no 
case, however, have the changes been sufficiently pronounced to account 
for the extensive degeneration in the posterior columns. The posterior 
roots are invariably degenerated. Some of the fibers are completely 
destroyed, others show disappearance of the myelin-sheaths and altera- 
tion of the axis-cylinders. Nageotte claims to have discovered a round- 



948 A TEXT-BOOK OF PATHOLOGY 

cell infiltration in the membranes surrounding the roots that causes a 
pressure degeneration. Redlich and Obersteiner believe that the 
changes are most marked after the entrance of the fibers into the cord, 
and explain this by supposing that there has been a slight constriction 
at the point where they pierce the pia mater. In this region there is 
certainly often considerable disappearance of the myelin-sheaths, but 
it cannot be said positively whether the intramedullary portion of the 
posterior roots is more degenerated than the extramedullary. 

Friedreich's Ataxia 

Friedreich's ataxia is a disease characterized by inco-ordination of 
the gait, the first symptoms coming on usually during puberty. It 
belongs to the hereditary type of diseases, occurs in successive gener- 
ations of the same family, and appears to have no other causation. The 
most constant change is hypoplasia of the spinal cord. This hypoplasia 
may be regular, so that the whole cord is three-fourths or even less of 
its normal diameter, or it may seem irregular in the latter instance, 
being, perhaps, more pronounced in the cervical and upper dorsal 
regions. Hypoplasia of the cerebellum is a frequent associated lesion. 
The two conditions are, however, rarely equal, and, according as one or 
the other preponderated, Marie described spinal and cerebellar forms 
of hereditary ataxia. The next most common lesion is degeneration 
in the posterior columns. This is particularly marked in the column 
of Goll, but, in severe cases, may also involve the column of Burdach. 
No degeneration at all may be found; such a case has been reported by 
Nonne; but in these instances the larger fibers are usually absent. 
Degeneration in Clarke's columns is not uncommon. In regard to the 
degenerative areas found in the lateral columns there is much difference 
of opinion. The majority of authors believe that they represent de- 
generation of the pyramidal columns, although it is certain that none 
of the clinical symptoms associated with this lesion are present. The 
degeneration is usually most pronounced in the lower part of the cord, 
diminishes in intensity upward, and disappears near the normal decus- 
sation of the pyramidal columns. According to Marie, the degener- 
ated areas usually lie to the outer side of the normal situation of the 
pyramidal columns. In all these degenerated areas there is consider- 
able proliferation of the neuroglia tissue, the fibers being especially 
increased, indicating the likelihood that the change is secondary. 
Other secondary changes are the thickening and partial adhesion of the 
pia mater, particularly that part in contact with the posterior columns 
of the spinal cord, and also the thickening of the walls of the blood- 
vessels, such as is usually found in sclerotic nervous tissue. Degenera- 
tion is also found in the posterior roots, which are smaller than normal. 
In regard to the condition of the peripheral nerves there is some differ- 
ence of opinion, but it seems certain that, in some cases at least, there 
is a degeneration of the sensory fibers. The disease partakes, therefore, 
of the nature of a combined sclerosis. Some authors hold that it is 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 



949 



due primarily to a hypoplasia of the third primary vesicle and of the 
neural canal — that is to say, the medulla, cerebellum, and cord. The 
disease, however, appears to be slowly progressive, and it is not evident 
in infancy. This may be explained by assuming that the hypoplastic 
central nervous system is sufficient for the needs of the child, and that 
as the organism develops it becomes relatively insufficient. This, how- 
ever, would not enable us to understand why such extensive secondary 
degenerations are sometimes present. 

Amyotrophic Lateral Sclerosis 

Amyotrophic lateral sclerosis is a disease which, theoretically, should 
present the following pathological changes: Degeneration in the pyra- 
midal columns, atrophy of the ganglion-cells of the anterior cornua, 




Fig. 435. — Multiple sclerosis. Second cervical cord. The spinal roots stain well and are 
not affected by the disease. 




Fig. 436. — Optic nerve, showing degeneration in central parts. (Photographs from the 
case illustrated in Fig. 437.) 

degeneration of the nerve-fibers in the anterior roots and of the motor 
fibers in the peripheral nerves, and degenerative atrophy of the muscles. 
The lesions that are actually found, however, are very various. Common 
to almost all cases is the atrophy of the motor cells of the spinal cord and 



950 



A TEXT-BOOK OF PATHOLOGY 




Fig. 437. — ^Transverse sections of the medulla and cord from a case of multiple sclerosis. 
Stained by Weigert's method. (Normal tissue colored dark, degenerated areas white.) 
1. Medulla. 2. Lower medulla. 3. Third cervical. 4. Fifth cervical. 5. Second dorsal. 
6. Sixth dorsal. 7. Twelfth dorsal. 8. First lumbar. The irregular areas of degeneration 
in different segments of the cord are not associated with secondary degeneration below or 
above the different lesions, except the degeneration in the posterior columns from the 
second dorsal up to the medulla (Burr and McCarthy). 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 951 

degeneration of their neuraxons, and the presence of compound granular 
cells, but there is no other sign of inflammatory reaction. The degen- 
eration of the ganglion-cells is usually extensive, and the muscles exhibit 
the changes characteristic of progressive spinal muscular atrophy — 
that is, swelling of the fibers, increase of the number of the nuclei, 
indistinctness of the striation, and increase in the amount of connective 
tissue, with, in the later stages, extreme atrophy of the fibers. The 
degree to which the pyramidal columns are affected is not constant; at 
times the degeneration is pronounced and extends as far as the internal 
capsule. Indeed, distinct alterations have been reported in the motor 
cortex of the brain — that is to say, degeneration of the ganglion-cells 
and the presence, in more or less considerable number, of compound 
granular cells. In other cases the degeneration may cease at a lower 
point, and in at least one case was not found at all. It has been sup- 
posed that in such cases there is only a slight alteration in the nutrition 
of the ganglion-cells, and that the degenerative changes commence at 
the peripheral portion of the neuraxon and advance cellipetally. The 
changes found in the pyramidal columns are, of course, similar to those 
occurring in the other primary degenerations. 

Chronic anterior poliomyelitis, or progressive spinal muscular 
atrophy, is strictly a degeneration of the peripheral motor neuron, and 
often appears to be hereditary in character. Otherwise no satisfactory 
etiology has ever been determined. It is characterized by gradual 
atrophy of the ganglion-cells of the anterior cornua and by diminution 
of the size of the cornua themselves. No lesions that distinctly indicate 
the existence of an inflammatory process are present. The cells gradu- 
ally grow smaller, become pigmented, and may ultimately disappear. 
There is degeneration of the fibers in the anterior roots and degener- 
ative atrophy of the muscles. The clinical course is slowly but irregu- 
larly progressive. The condition in many respects resembles amyotrophic 
lateral sclerosis, and cases have been recorded in which other degenera- 
tions were found, particularly in Clarke's column and in the posterior 
columns. The lesions apparently commence in the cervical region, and 
may later extend to other parts of the cord, and even to the motor 
nuclei of the medulla. This last causes so-called bulbar, or glossio- 
labiolaryngeal palsy, which follows the clinical and pathological char- 
acters of the rest of these affections with limitation of the lesions to the 
medulla, with perhaps an added degeneration of the pyramidal tracts. 
There is a form of chronic poliomyelitis in which distinct lesions of the 
vessels are present, and which is apparently only a slow form of the 
ordinary acute poliomyelitis. 

Combined sclerosis, giving rise to ataxic paraplegia, has been de- 
scribed in a great number of instances, and a characteristic symptoma- 
tology has been ascribed to the condition. Usually the parts affected are 
the posterior columns, the columns of Clarke, and, in part, the lateral 
pyramidal tracts. The lesions do not differ in appearance from those 
of the other forms of primary degeneration. The areas are gray, some- 
what shrunken, and contain an excess of neuroglia, granular cells, and 



952 



A TEXT-BOOK OF PATHOLOGY 



amyloid bodies. The nature of the process is still undecided. The 
frequency with which a certain definite combination occurs has led some 
neuropathologists to believe that it is a morbid entity. Others, how- 
ever, contend that the parts of the cord affected are. those least able, 
on account of their poor blood-supply, to resist noxious influences, and 
that, therefore, the disease is only the reaction of the weaker parts of 
the spinal cord to a general morbific agent. The disseminated or mul- 
tiple sclerosis are commonly associated with similar lesions in the brain, 
and have been described under that heading (p. 915). 

Lateral sclerosis, with exclusive involvement of the lateral columns 
connected with the motor cortex or upper neuron, is very rare in a pure 
form. There is retained muscle tone because the trophic cells in the 
gray matter of the cord are not attacked. At first there is spasticity 
and, later, paralysis of the affected muscles. 

Degenerations in the white matter of the spinal cord have 
been described in various forms of chronic anemia, especially pernicious 
anemia. Two varieties can be distinguished, those in which the areas 
of sclerosis are disseminated irregularly through the cord, and those 




1.2 3 
Fig. 438. — Sections from a case of ataxic paraplegia, showing system degeneration of 
the posterior column, lateral (crossed), pyramidal, and direct cerebellar tract: 1, Cervical, 
2, lumbar; 3, sacral (Burr and McCarthy). 

in which the degeneration is systemic in nature and follows more or 
less closely the area of distribution of the fibers of the posterior root. 
In the latter case the posterior columns are affected most severely, and 
the lesions are most pronounced in the cervical region. Degeneration, 
however, may also be found in the lateral columns, either involving 
only a small patch of fibers, or so extensive as to give rise to the appear- 
ance of combined sclerosis. The degeneration appears to occur primar- 
ily in the nerve-fibers, with secondary proliferation of the neuroglia. 
Vascular changes, particularly minute hemorrhages and thickening of 
the vessel walls, are also found, and when present the nerve-fibers in the 
immediate vicinity of the vessels are often degenerated. These changes 
are not, however, found in all cases of progressive pernicious anemia, a 
number of cases being now on record in which the spinal cord showed 
no trace of degeneration. No satisfactory explanation has hitherto 
been given to account for them. It has been suggested that the anemias 
with spinal lesions belong to a different group, but this is, of course, a 
mere hypothesis. The absence of degeneration in the posterior roots 
seems to exclude a peripheral neuritis, although it is possible that in 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 953 



case of slight disease of a spinal ganglion the terminations of its nerve- 
fibers in the medulla would exhibit the first trace of degeneration, and 
this, in fact, corresponds with the condition found in some of the cases. 

Similar changes have also been found in other conditions, especially 
the chronic cachexias, such as tuberculosis, diabetes, and carcinoma. 
Changes occurring in the spinal cord in ergotism and pellagra have been 
described. In the former the areas of degeneration are said to be chiefly 
in the posterior columns, limited, excepting in the cervical regions, to 
Burdach's column, and there are lesions in the posterior roots. In 




3 

Fig. 439. — Descending degeneration of direct and crossed pyramidal tracts following 
hemorrhage into the medulla: 1, Dorsal region; 2, lumbar region; 3, cervical region 
(McCarthy and Pearce). 

The lesions presented in the above sections are confined to the motor system, and 
caused a spastic type of paralysis without sensory derangement. 

pellagra degeneration is found in Goll's column, particularly in Bur- 
dach's column, and usually in the lateral columns also. There are 
also partial disappearance of the cells of the anterior cornua and small 
degenerative foci in the anterior columns. Changes limited to the poste- 
rior column have also been noted after diphtheria and leprosy. In old 
age small, irregular areas of degeneration, particularly in the posterior 
median column, and sometimes at the periphery of the spinal cord, may 
be observed. 

SECONDARY DEGENERATIONS OF THE CORD 

Secondary degenerations of the spinal cord occur after any lesion 
interrupting the course of one or more of the columns of fibers, and also 
after any disease of the ganglion-cells that nourish these fibers. They 



954 A TEXT-BOOK OF PATHOLOGY 




1. Degeneration of the posterior columns in pernicious anemia. 




2. Diffuse anteroposterior and lateral degeneration of cord in a senile case of progressive 

pernicious anemia. 




3. Diffuse degeneration of cord in intense anemia associated with chronic parenchymatous 

nephritis (cervical cord). 

Fig. 440, 1, 2, and 3 present the diffuse toxic lesions met with in anemic and cachectic 
conditions. The degeneration is diffuse, not confined to any particular tract of the cord, 
but usually predominating in the posterolateral areas. It is not infrequently referred to 
as posterolateral sclerosis. No. 1 is from an early case, and shows the relation of the 
degeneration to the arterial supply of the posterior columns. 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 



955 



have been divided into ascending and descending, according to the 
direction in which the degeneration proceeds. It will be clear from the 
description already given of the course of the columns of the cord that 
the chief variety of descending degeneration will be that of the pyram- 
idal columns. This may occur as a result of injury to the motor cortex, 
or of interruption of the motor fibers in any part of their course from 
the cortex to the conus terminalis. If the lesion is unilateral and above 
the decussation, ordinarily only one pyramidal column is distinctly 
affected — that is to say, the anterior pyramidal tract of the same side 
and the lateral pyramidal tract of the opposite side. Careful micro- 
scopical investigations, however, have shown that certain fibers that do 
not decussate pass down the spinal cord in the lateral columns. In 




Fig. 441. — Sclerosis of the white substance of the cord. 



cases of long-standing secondary degeneration of the pyramidal columns 
a certain amount of simple atrophy of the ganglion-cells of the anterior 
cornua has been observed. Descending degeneration has also been 
observed in the posterior columns. In the upper portion of the cord 
it assumes the form of two small areas that project from a point slightly 
posterior to the gray commissure and extend backward and outward. 
This has been called the comma degeneration of Schultze. In the lower 
part of the cord these descending fibers appear to approach the posterior 
commissure and form the oval field of Flechsig. Descending degenera- 
tion for a short distance below a total transverse lesion may be found 
in all the columns. Ascending degeneration occurs chiefly in the poste- 
rior columns, and is described in connection with tabes dorsalis. In 



956 



A TEXT-BOOK OF PATHOLOGY 



case of isolated injury to one of the posterior roots, there may be traced 
upward a slender band of degeneration that gradually approaches the 
posterior septum. Ascending degeneration also occurs in the direct 




Fig. 442. — Acute gliomatous degeneration of the spinal cord, showing relative size of cord 

in different localities. 

cerebellar tract, and may often be found to be associated with disease 
of the ganglion-cells in Clarke's columns. It extends as far as the 
restiform bodies in the medulla. Ascending degeneration also occurs 




Fig. 443. — Highly magnified section of the cord from the same case. The white areas 
correspond to an active proliferation of the neuroglia cells with destruction of the myelin- 
sheaths. The neuroglia cells act as scavenger cells in this destructive process. There was 
no secondary degeneration below the cervical cord. The disease ran an acute course 
and presented an ascending type of paralysis (McCarthy and Pearce). 



in the anterolateral tract of Gowers. After total transverse lesion 
secondary alterations may usually be detected in the remote portions 
of the cord in the course of from five to seven days. These alterations 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 



957 



consist of a swelling of the axis-cylinders and, within a very short time, 
fatty degeneration of the myelin-sheaths. Granular cells appear early 
in the tissue. In the course of a month the degenerative changes are 
quite pronounced, and may readilv be detected by Weigert's method. 
The myelin-sheaths have disappeared wholly or in part; the axis- 
cylinders have also vanished, although some varicose fibers may be 
found here and there in the lesion. Compound granular cells largely 
fill the field, but there is also a distinct hyperplasia of the neuroglia 
tissue, giving the area, macroscopically, a somewhat grayish appearance. 
Still later, contraction begins to occur and the appearances seen in the 
primary degenerations are found. 

TUMORS 

Glioma. — Of the primary tumors of the spinal cord, the most fre- 
quent and important is glioma. This is usually infiltrating in type 
and elongated, extending for a distance of several segments along the 
cord, and sometimes involving the nerve-roots, causing them to swell 
and become harder. It may give rise to curious distortions in shape, 
and an apparent hypertrophy; this latter is probably the result of the 
compression in a longitudinal direction of some portion of the cord, 
so that in a given section more ganglion-cells are found than would 
normally be present. 

Proliferation of the neurogliar tissue of the cord, causing increase 
in size of the segments affected — often without, however, distinctly 
injuring the normal tissue of the cord — may be produced by pressure 
on the outside or by interference with the circulation. It occurs in 
cases of tumor of the membranes or of the spinal column, in disease of 
the spinal column, and in pachymeningitis. The neuroglia tissue fre- 
quently contains, in addition to the increase in the number of fibers, 
huge multipolar cells that have been described in true gliomata by 
Stroebe. 

Sarcoma alone, or containing gliomatous or mucoid tissue, or of 
the type known as angiosarcoma, may also appear. 

Carcinoma and sarcoma may also appear as metastatic growths. 

Cysts are exceedingly rare, but both the echinococcus and the 
Cysticercus cellulosce have been reported. 



CHAPTER XIV 



DISEASES OF THE PERIPHERAL NERVOUS SYSTEM 

The Ganglia of the Cranial and Spinal Nerves 

The ganglia of the spinal nerves may be diseased as a result 
of extension of pathological processes, usually tuberculosis, from the 
surrounding bony structures. It is probable that they are also subject 
to inflammatory changes. Spiller and Keen have reported the results 
of the examination of a number of Gasserian ganglia removed on ac- 
count of persistent trifacial neuralgia, in which they found degeneration 
— in some cases total — of the myelin-sheaths and the nerve-fibers in the 
ganglia. In one case the degenerated nerve tissue was replaced by 
connective tissue, giving rise to marked sclerosis. Occasionally the 
cells in the ganglia had undergone atrophy, and in all instances the 
vessels were distinctly sclerotic, the lumen being sometimes completely 
obliterated. The authors believe that these changes are not primary, 
but secondary to lesions in the peripheral sensory nerves. 

The spinal ganglia may also be diseased. Slight degenerative 
changes have been noted in locomotor ataxia and as a result of periph- 
eral neuritis. In this case the walls of the ganglia show swelling and 
granulation of the chromatin bodies, and are often somewhat shrunken. 
More frequently the ganglia are involved as a result of disease of the 
surrounding bones; particularly caries or sarcoma of the spine may 
produce pressure, resulting in atrophy, or, in the case of the former, 
areas of tuberculous softening. The ganglia of the spinal nerves are 
sometimes found diseased in cases of herpes zoster, and are supposed to 
have an etiological relation to that disease. Zinno has reported a case 
in which there appears to have been a chronic swelling of the ganglia, 
some of which were as large as a pigeon's egg, as a result of a hyperplasia 
of the neuroglia and the connective tissue. These swollen ganglia 
pressed upon the cord and produced secondary degenerations. Enlarged 
spinal ganglia have also been observed in acromegaly. 

The Nerves 

circulatory disturbances 

Hyperemia of the nerve-trunks attends acute inflammations. The 
vessels of the perineurium may be intensely injected. 

Hemorrhages may result from acute congestion or from traumatic 
injuries. They take the form of punctate ecchymoses in the perineurium 
or endoneurium. 

Edema of the nerve-trunks may occur in the nerves traversing areas 
of inflammation. 

958 



DISEASES OF THE PERIPHERAL NERVOUS SYSTEM 



959 



ATROPHY AND DEGENERATION 

Atrophy of the nerves occurs in consequence of pressure upon the 
nerve or as a result of disease (neuritis) of the nerves. It may also 
result from disease of the central nervous system, causing disturbance 
or destruction of the nuclei of origin of the peripheral nerves. Occa- 
sionally atrophy arises without definite cause in old age. The changes 
in the nerve are similar to those following section of the nerve, and are 
described under the heading Degeneration. 

Degeneration. — Injury of a nerve in its course produces various 
manifestations in the nerve-fibers corresponding more or less to the 
nature of the destructive agencies. It is obvious that if the nerve be 
divided by a clean incision, the degenerative changes below the point 
of incision will be less extensive than if the destructive agent is severe, 
such as in cauterization, the crushing of the nerve-trunk with extensive 
disintegration, or the removal of a section of some length. Still milder 
changes, however, may be produced by a ligature that is not drawn 
tightly enough to destroy completely all the nerve-fibers. Degenerative 
changes are less pronounced if there is prompt coaptation of the injured 
ends, or if the continuity of the nerve is not entirely destroyed. 

If a nerve is examined immediately after injury, there will be found 
only deformity of the nerve-fibers. This consists in dislocation of the 
myelin and perhaps fibrillation of the axis-cylinder, so that it seems 
to be crushed into and diffused throughout the white substance of the 
nerve-fiber. Within a few hours the cells in the myelin-sheath begin to 
exhibit signs of degeneration, the chromatin swells, stains more feebly, 
and may undergo fragmentation. At the end of eighteen hours the axis- 
cylinder is usually slightly swollen and its outline becomes irregular. 
These changes, however, are by no means uniform throughout the whole 
, nerve, some parts perhaps being almost normal and others extensively 
degenerated. At the end of thirty-six hours the myelin substance has 
undergone fatty degeneration, with the formation of small globules. 
These changes are found on both sides of the lesion, on the proximal 
side extending to the first node of Ranvier, and on the peripheral side 
extending considerably beyond this. At first the changes in both frag- 
ments are approximately equal, but those in the peripheral end rapidly 
progress and soon dominate the field. The changes in the peripheral 
fragment, however, are more pronounced near the lesion and diminish 
toward the periphery. In the central end there are nearly always a few 
fibers that degenerate as far as the spinal cord, but these are the excep- 
tion. 

REGENERATION AFTER INJURY OF A NERVE 

The first sign of regeneration is proliferation of the cells of the 
sheaths. Their nuclei exhibit karyokinetic figures, and there appears 
to be an increase in their protoplasmic substance. At the same time 
the cells of the connective tissue also undergo multiplication and, to a 
certain extent, act as phagocytes, absorbing the fatty detritus. The 



960 



A TEXT-BOOK OF PATHOLOGY 



protoplasm of the cells of the sheath gradually elongates and occupies 
the situation of the myelin substance and the old axis-cylinder. There 
appears to be some doubt whether these changes are more pronounced 
in the proximal or distal fragments; at any rate, the protoplasm of the 
cells of the sheaths on both sides of the lesion seem to possess phagocytic 
properties and to absorb some of the fat and detritus resulting from the 
degenerative changes. The protoplasmic mass usually closes the free 
ends of the nerve-fibers, and assumes a somewhat conical form, not 
unlike a node of Ranvier. This mass appears to be continuous with the 
partially degenerated end of the axis-cylinder. Toward the end of the 
first week the elongated protoplasmic masses in the end of the nerve- 
fibers become somewhat differentiated. In the interior may be seen a 
delicate fibrillated structure that appears to be continuous with the 
axis-cylinder of the nerve; outside of this is a delicate membrane, but 
both of these structures lie within the old myelin-sheath, in as far as 
it is preserved. It is probable that mildly damaged axis-cylinders, or 
those with a moderate grade of chromatolysis, can regenerate, but when 
the injury is severe or the nerve-fiber completely severed and separated 
it is not likely that union of the segments results. Both the proximal 
and peripheral fragments of the axis-cylinder degenerate and a new one 
must grow from the cell. Axis-cylinder regeneration must, of course, 
be preceded or accompanied by processes in the sheath and neurilemma. 
As the new nerve-fibers increase in length they gradually pass through 
the injured area and come in contact with the proximal area of the 
peripheral fragment. In this the cells of the sheath have undergone 
proliferation and have formed protoplasmic masses at the ends of the 
fiber. Differentiation in this protoplasmic mass does not, however, 
appear to occur until the new axis-cylinder reaches it. Gradually the 
nerve approximates more and more closely to the normal appearance, 
the axis-cylinder becoming more distinct and the myelin-sheath thicker 
until it can be said to be re-established. In the course of the absorption 
of the fatty and other detritus, cells that are filled with fat-droplets 
accumulate in the connective tissue of the nerve and between the fibers, 
which are probably ordinary compound granular cells. It is question- 
able, however, whether they are derived from the endothelium of the 
lymph-spaces or from the leukocytes, or whether they represent the 
excess of the proliferated cells of the sheath. Somewhat later, con- 
centric masses may be found that resemble very closely the amyloid 
or hyaloid bodies of the central nervous system. 

INFLAMMATIONS 

Neuritis may be either acute or chronic. It has also been classified 
as parenchymatous and interstitial ; the former comprising the degenera- 
tions of the nerve-fibers without involvement of the connective tissue, 
and the latter comprising all those forms associated with the character- 
istic signs of an inflammatory process in the connective tissue of the 
nerve. 



DISEASES OF THE PERIPHERAL NERVOUS SYSTEM 



961 



Acute interstitial inflammation, or neuritis proper, may be caused 
by direct extension from an inflammatory focus in the surrounding 
tissue or by trauma, or as the result of some as yet unknown poison 
which is generally supposed to be rheumatic in nature. It may also 




Fig. 444. — Neuritis: longitudinal section, showing degenerated nerve-fibers (black); 

Azoulay's method; X 300. 



occur in the course of acute infectious diseases, or as an independent 
condition, as in beri-beri. The inflammatory changes occur in the 
perineurium and the endoneurium. The nerve is swollen, soft, and 
pinkish in color. Microscopically, both the perineurium and the 




Fig. 445. — Chronic hypertrophic interstitial neuritis; X 100 (case of Dejerine). 

trabecular of connective tissue are increased in size, the blood-vessels are 
distended, and there is extensive round-cell infiltration. In the acute 
forms partially degenerated fibers with fatty myelin-sheaths and swollen 
axis-cylinders are found very early. The primary change unques- 

61 



962 



A TEXT-BOOK OF PATHOLOGY 



tionably occurs in the connective tissue, and the nerve-fibers are in- 
volved secondarily, the myelin-sheaths being the parts first affected. 

Chronic interstitial neuritis may follow the acute form or com- 
mence as an independent condition. The nerve is harder than normal, 
the connective tissue is increased, the walls of the blood-vessels are 
thickened and their lumina may be partially obliterated. More or 
less round-cell infiltration is found in the hyperplastic connective tissue, 
and the nerve-fibers show extensive degeneration, many of them having 
disappeared, and the few that remain presenting marked morbid changes. 
Often there is a distinct proliferation of the cells in the neurilemma. 
This form of neuritis in particular is associated with muscular degenera- 
tion, and appears to give rise to the type known as the neural form of 
progressive muscular atrophy. Associated changes are often found in 
the spinal cord, and consist of an ascending degeneration in the posterior 
columns and more or less alteration of the ganglion-cells. In a variety 
of this disease, described by Dejerine under the name of chronic hyper- 
trophic interstitial neuritis, there is an actual overgrowth of the con- 
nective tissue, the nerve-trunks forming huge, firm cords, several times 
the normal thickness, that may readily be felt beneath the skin. This 
disease is apparently due to some hereditary familial influence. Micro- 
scopically, the changes consist of an enormous proliferation of the 
connective tissue with round-cell infiltration, partly about the sclerotic 
blood-vessels, and pronounced degeneration of the nerve-fibers. The 
muscles undergo degenerative atrophy, and there are secondary degen- 
erations in the spinal cord. 

Suppurative neuritis is nearly always secondary to suppuration in 
the tissue surrounding the nerve. It is characterized by the presence 
of small foci of pus in the connective tissue and softening of the nerve- 
trunk. The nerve-fibers degenerate very rapidly. 

Parenchymatous neuritis is characterized by a primary degenera- 
tion of the nerve-fibers, the alterations in the connective tissue being 
secondary. It is always due to some toxic or infectious substance cir- 
culating in the fluids of the body. The most common causes are lead, 
arsenic, alcohol, and diphtheria; but it also occurs as a result of other 
poisons and infectious diseases, and in the course of tabes dorsalis. The 
nerve-trunk becomes slighter, firmer, and grayer. Inflammatory changes 
are slight or absent, while the degeneration of the nerve-fibers is pro- 
nounced. Changes have frequently been found in the cells in the ante- 
rior cornua of the spinal cord. 

Polyneuritis does not differ from the isolated form, excepting that a 
number of nerve-trunks in various parts of the body, usually the limbs, 
are affected at the same time. It is most frequently of the parenchy- 
matous type. 

INFECTIOUS DISEASES 

Tuberculosis of the nerve-trunks is due to direct extension. It 
most commonly affects the roots of the nerves, and occurs in the course 
of tuberculous spinal or cerebral pachymeningitis. The connective tissue 



DISEASES OF THE PERIPHERAL NERVOUS SYSTEM 



963 



is first affected, and may contain small cheesy foci, in which epithelioid 
and giant cells are found. The nerve-fibers degenerate secondarily. 

Syphilis also occurs, chiefly in the nerve-roots. It causes over- 
growth of the connective tissue, particularly in the perineurium, with 
pressure upon and degeneration of the nerve-fibers. Gummata are 
sometimes observed upon the cranial nerves. 

Leprosy is characterized by the presence, in the connective tissue 
of the nerve-fibers, of large epithelioid cells containing vacuoles more or 
less filled with lepra bacilli. The bacilli cause a certain amount of 
hyperplasia of the connective tissue, which presses upon and eventually 
destroys the nerve-fibers. The disease affects the small cutaneous 
nerves almost exclusively, and causes anesthesia and trophic changes 
in the skin. 

TUMORS 

Neuroma. — The tumors embraced by this term have been suffi- 
ciently described under the heading Neuroma, in Part I. 

Sarcoma is a rare tumor of nerve-trunks. It takes its origin from 
the connective tissues of the nerve. 

Muscle=fibers are sometimes found in intramuscular nerve- 
trunks. They usually exhibit proliferation of the nuclei, but the stria- 
tions remain distinct. Their position has been ascribed to errors of 
development, but it is not certain that they are without function. 



CHAPTER XV 



THE EYE 
ANATOMY 

The Conjunctiva. — This is a sac lined with stratified epithelium 
covering the exposed portion of the eyeball and reflected to the lids, at 
the margin of which it becomes continuous with the skin. When this 
sac is dissected off and spread out it is as large as the palm of the hand. 
Upon the inner surface of the lids and upon the ball there is squamous, 
near the canthus, columnar epithelium. In the latter situation goblet- 
cells abound. Beneath the epithelium is a loose areolar and adenoid 
layer and then a thick connective-tissue layer, the so-called tarsal car- 
tilage which contains the Meibomian glands. The subepithelial layer 
upon both lids and ball is loose but highly vascular. 

The lachrymal apparatus consists of a compound racemose gland 
lying in the upper outer portion of the orbit, discharging tears through 
two ducts into the lachrymal sac at the internal canthus, by the lachry- 
mal puncta near the caruncle. The tears are expressed from this sac by 
the contraction of the palpebral sphincter and forced into the nasal 
duct. They are spread over the conjunctival surface by nictitation. 

The cornea is a transparent avascular epithelial structure continuous 
at its margin with the sclera. From without inward there is first a 
squamous epithelial layer continuous with the epithelium of the con- 
junctiva, covering the acellular outer capsule, or Bowman's membrane. 
The body of the cornea is composed of lamellated epithelium com- 
parable to the horny epidermis, between the layers of which course 
lymph-channels; the interstitial branched cornea cells lie in lacunae. A 
hyaline internal capsule (Descemet's membrane), lined on the surface 
of the anterior chamber by a single layer of endothelium, constitutes 
the innermost part of the cornea. The cornea is without blood-vessels, 
nutrition being derived from vascular plexuses at its juncture with the 
sclera. The two internal layers join with the structures of the uveal 
tract. 

The sclera is the stiff external capsule of the eyeball, composed of 
variously arranged bundles of white connective tissue with some yellow 
elastic fibers. 

The lens is a transparent convex epithelial body lying immediately 
behind the iris, surrounded by an acellular capsule thickest anteriorly. 
The body is formed of homogeneous fibers which grow from the capsule 
of the equator and the portions just anterior to this zone, the origin 
of these fibers being a layer of transparent polygonal cells lying below 
the lens capsule. The older fibers are pressed toward the center to 

964 



THE EYE 



965 



form a nucleus. The lens is held in position by fibers from the ciliary 
body. 

The vitreous humor is a soft, gelatinous, clear, colorless tissue occupy- 
ing the center of the inner eye. It contains a few leukocytes and 
branching cells, the processes of the latter are attached to the delicate 
vitreous capsule and form the supporting structure. 

The iris, ciliary body, and choroid form the uveal tract. The first 
consists of an anterior and posterior layer of endothelium beneath which 
is a hyaline layer. The endothelium in front is continuous with Des- 
cemet's membrane, that posteriorly extends into the choroid over the cil- 
iary processes. The central layer contains radiate and annular muscle- 
fibers which find their origin and support in the ciliary body. In this 
fibromuscular area are cavernous lymph-spaces for the entrance and exit 
of the aqueous humor which is produced by the ciliary processes. The 
aqueous humor, a fluid occupying the spaces in front of the lens, is a 
modified lymph without leukocytic content, containing a very low per- 
centage of protein and sugar. The last is in greater amount than in 
the blood-serum, and varies directly as this latter, except in diabetes, 
when the sugar content is relatively very high. The choroid is the poste- 
rior extension of the ciliary body and extends to the opening for the optic 
nerve. The anterior part is supplied with blood by the ciliary branches 
of the vessels supplying the ocular muscles, the posterior part by the 
vessels in the optic nerve, and these two sets anastomose. 

The Retina. — This layer of the eye is the specialized end-organ of 
the optic nerve. It spreads from the nerve-head to the ciliary body. 
It consists from the choroid inward of a pigmented layer upon which 
lies the neuro-epithelial layer of rods, cones, and fibers, which latter is 
separated from the nuclear, ganglion, and nerve-fiber layer by a dense 
neurofibrillar layer. The retina is limited internally by a condensation 
of nerve-fibers arising in the deeper layers. 

The eye lies in the anterior part of the orbit supported by fat and 
muscles. 

CONGENITAL ABNORMALITIES 

Anophthalmia is complete absence of the eye, a rare condition ; while 
microphthalmia, abnormal smallness of one or both eyes, is more com- 
mon. Abnormalities due to formations in defectu comprise: synoph- 
thalmia, or cyclopia, a condition in which the prosencephalon fails to 
divide correctly, a single orbit and eye resulting; cryptophthalmia, in 
which the bulb is hidden by failure of the lids to divide. The lids show 
as the most frequent abnormalities: coloboma, an angular defect with 
its base on the free margin; congenital ptosis, and epicanthus, a fold of 
skin passing across the inner canthus from the upper to the lower lid. 

THE CONJUNCTIVA 

Circulatory • Disturbances. — Anemia of the conjunctiva alone is 
an unusual condition, but pallor is common in general anemia. 



966 



A TEXT-BOOK OF PATHOLOGY 



Hyperemia is common, and has as its chief cause external mechanical 
irritation, foreign bodies, or gases. It may be a sign of errors of refrac- 
tion, depending upon physical changes in the eye. It is present as an 
early stage of inflammation. 

Hemorrhage beneath the membrane may occur from traumatism, 
or by undue muscular effort in the presence of diseased vessel walls. 

Edema occurs as part of general edema, or as a result of local venous 
obstruction, and in infections of neighboring sinuses. 

Degenerations of the conjunctiva are rare, but homogeneous 
metamorphoses have occurred in edematous hyperplastic lesions of the 
epithelial, areolar, and adenoid layers, to which the names colloid and 
hyaline or even amyloid degeneration have been given. 

Inflammations. — Conjunctivitis may be primary or secondary; the 
latter arising by extension, or occasionally by infection via the blood- 
stream. Prolonged irritation by mechanical or chemical agents may 
occasion a true inflammation, but to these factors is almost invariably 
added the action of bacteria, of which many different forms have been 
noted. The principal ones are Morax-Axenf eld's organism, Koch- 
Weeks' bacillus, gonococcus, pneumococcus, diphtheria and pseudodiph- 
theria bacillus, Micrococcus catarrhalis, streptococcus, Bacterium xerosis, 
and Bacillus coli. The pathological changes are congestion and edema 
of the subepithelial layer, followed by hyperplasia of the adenoid tissue 
and infiltration. The epithelium is swollen, softened, becomes opaque 
and desquamates, leaving erosions or ulcerations. The process may be 
catarrhal, or exudative — serous, purulent, or pseudomembranous. There 
are several special forms of inflammation hypertrophic in character, 
such as trachoma, which may be classified as subacute or chronic. 

Acute Catarrhal Conjunctivitis. — In this condition there is swelling, 
redness, and a profuse thin discharge, arising to some extent from the 
diseased membrane, but chiefly from the overproduction of tears. The 
redness is greater at or near the canthi. The process may go over into 
acute purulent conjunctivitis, in which the discharge is purulent almost 
from its inception. The gonococcus is the commonest cause of the 
frank purulent conjunctivitis, particularly in the newborn. The con- 
junctiva and lids in this case are much swollen, and hemorrhages may 
occur, and there is a profuse yellow or greenish discharge. This form 
of inflammation frequently spreads to the cornea or uveal tract. 

Pseudomembranous conjunctivitis is usually due to the diphtheria 
organism, but may be caused by other germs. There is much infiltra- 
tion and induration of the subepithelial tissues, and upon the surface a 
patchy or continuous membrane may form, beneath which ulcers arise. 

Special Forms. — Spring catarrh, or vernal conjunctivitis, is a 
chronic recurring hypertrophic inflammation of unknown cause, char- 
acterized by the production of rather flat excrescences upon a smooth, 
hard conjunctiva. The appearance of the surface is as if a thin film of 
milk were spread upon it, a condition said to be due to hyalinization 
below the epithelium. The excrescences are made up of hyperplastic 
epithelium and connective tissue, the latter being quite homogeneous or 



THE EYE 



967 



hyaline; in this overgrowth eosinophils are common. Ulcerations sel- 
dom appear in this disease. The secretion is tenacious, yellowish, 
and may be very profuse. 

Follicular conjunctivitis is a subacute or chronic, slightly com- 
municable hypertrophic inflammation characterized by hyperplasia of 
lymphatic tissue producing elevated granules or follicles, usually follow- 
ing the course of the conjunctival folds. This seldom leads to any cica- 
trization, although there is a sort of capsule about the lymph-follicles. 

Trachoma is a chronic communicable hypertrophic conjunctivitis 
characterized by the production of papillary granulations, connective 
tissue overgrowth, and cicatrization, with signs of mild exudative in- 
flammation. These growths appear chiefly upon the lid and at the 
fornix, and contain the so-called "trachoma bodies," nodules of hyper- 
plastic lymphatic tissue surrounded by a fibrous and vascular capsule. 




Fig. 446. — Trachoma, showing round, opaque bodies in upper and lower lids. "Sago- 
grain" type. From a photograph. Frequent type seen in children (Henry T. Brooks). 

The marginal zones of the "bodies" are small and lymphoid, while in 
the center there are large lymphoid cells with granular nuclei, and 
frequently the trachoma "cell inclusion," a hyaline body with a bit 
of chromatic material in it. By some these are said to be like dip- 
lococci. Most observers now put them among Prowaczek's Chlamy- 
dozoa, w T hile some place them among the Protozoa. Many doubt their 
etiological relation, as they have been seen in gonorrheal conjunctivitis. 
Influenza bacilli or closely associated species have been found in 
trachoma. At all events, the cause of the disease is not yet known, 
and most observers believe that the infective agent belongs to the 
filterable viruses. Attempts at cultivation resulted in the develop- 
ment of minute bodies of indefinite morphology. The virus is 
present in the tears, and seems infective at any time in the course of 
the disease. It is infective for monkeys. Exposure to a temperature of 



968 



A TEXT-BOOK OF PATHOLOGY 



56° C. for thirty minutes or to drying for one hour destroys the 
virus. 

The "trachoma bodies" undergo cicatrization and involve the 
whole lid, and sometimes the bulbar layer, even to the production of 
entropion in the former, or pannus (granulation tissue) in the cornea. 

Pannus is a hyperplastic vascularizing growth of the surface of 
the cornea due to superficial ulcerative processes. The chief causes 
are trachoma and phlyctenular disease. The lesion proceeds from the 
limbus inward, lying between the epithelium and Bowman's mem- 
brane, and consisting of cellular infiltration and capillaries, the former 
preceding the latter. When Bowman's membrane is destroyed the 
corneal matrix is infiltrated and opacity results. » 

Parinaud's conjunctivitis is a severe condition with considerable 
swelling and papillary granulations on the tarsal layer, associated 
with signs and symptoms of general infection. The disease has been 
ascribed to a leptothrix, to be found in areas of necrosis in the sub- 




d 

Fig. 447. — Trachoma of the retrotarsal fold: a, Follicle; b, diffuse infiltration; c, Henle's 
gland with goblet-cells; d, lymph-vessel filled with leukocytes; X 30 (Holden). 

epithelial tissues. An enlargement of the preauricular glands occurs 
so often in this condition that it acquires a diagnostic significance. 

"Pink-eye" is an acute catarrhal and mucous conjunctivitis due to 
the Koch-Weeks' bacillus. 

Angular conjunctivitis is a contagious condition due to the diplo- 
bacillus of Morax and Axenfeld, characterized by scanty discharge, 
congestion of the caruncle, and, microscopically, by epithelial multipli- 
cation and desquamation on the tarsal side, with ingrowth thereof at 
the edge of the cornea. 

Phlyctenular conjunctivitis is now believed to be an atypical tuber- 
culous process, and is commonly found in association with tuberculosis 
elsewhere. It is also frequently associated with eczema. There are 
small papules or pustules, formed by the accumulation of lympho- 
cytes under the epithelium, which may become pustular, or break 
down to become ulcers. The condition is commonest on the bul- 
bar layer, and the cornea is frequently involved. 



THE EYE 



969 



Xerosis is a condition of chronic , atrophic inflammation and cica- 
trization of the bulbar conjunctiva. The two layers may be bound 
together, and there is frequently a dry scaly membrane on the free 
surfaces. It is said to be due to the Bacterium xerosis, but this is by 
no means accepted by all ophthalmologists. 

Tuberculosis is usually secondary to tuberculosis in the vicinity, 
but may be primary, as a miliary tubercle or small ulcer. Occasionally 
caseous masses occur, or a hypertrophic lesion like lupus may arise. 

Syphilis. — Characteristic lesions of all three stages have been seen 
in the conjunctiva. 

Pinguecula. — This is a pale yellow triangular chronic thickening 
of the conjunctiva at the margin of the cornea. This is not a mass of 

fat, but a proliferation of yel- 

low elastic tissue, and a hyaline T 




Fig. 448. — Phlyctenular conjuncti- Fig. 449. — Symblepharon, the sequel of 

vitis (Children's Hospital) (de Schwei- purulent conjunctivitis (from a patient in the 
nitz). Philadelphia Hospital) (de Schweinitz). 

of the conjunctiva in triangular shape, proceeding from the palpebral 
fissure toward the center of the cornea. It is probably due to con- 
tinued local irritation. Destruction of Bowman's membrane and 
opacity of the cornea results. The fold is made up of epithelia, beneath 
which are lymphoid cells and new blood-vessels. 

Symblepharon is the adhesion between the bulbar and tarsal 
conjunctiva due to continued irritation or chronic inflammation. It is 
a frequent sequel of burns. 

Tumors. — Fibromata, papillomata, and lipomata are among the 
common benign growths, and teratomata have been seen. Angiomata 
are common in early life, and may be either simple nsevi or of a sar- 
comatous nature. Sarcomata are not common, but develop from pig- 
mented spots at the edge of the cornea. They are exceedingly vascu- 
lar. The most interesting one is the alveolar sarcoma, or endothelioma, 
which some observers consider epithelial in nature. Epithelioma is the 
commonest tumor in this locality, and is a rapidly growing squamous 
cell growth. Carcinoma may arise from the caruncle. 

Cysts may be lymphangiectatie, or as the results of obstruction to 
glands. Occasionally cysts arise by invagination of epithelium in the 



970 



A TEXT-BOOK OF PATHOLOGY 



submucous tissue by reason of inflammation or injury. Such folded-in 
cells continue to secrete fluid and cause cystomata. Cysticercus and 
filarial cysts have been observed. 

LACHRYMAL ORGANS 

The lachrymal sac may be the seat of acute inflammation {dacryo- 
cystitis) by extension through the ducts, by injury, or rarely, primarily. 
Inflammation, either acute or chronic, may obstruct the flow of tears 
and distend the sac. Chronic inflammation around the canthus is 
usually associated with inflammation of the nasal duct and obstruction 
of tears. Inflammation of the nasal duct may be an extension process 
from the nose. Occlusion of the duct is temporary in acute inflam- 
mations, but stenosis may occur as the result of long-standing nasal dis- 
ease. Dacryo-adenitis, or inflammation of the lachrymal gland, is of 
any form, and arises from injury or by extension from the conjunctiva 
upward along the canaliculi. 

CORNEA 

Keratitis, or inflammation of the cornea, is usually primary, but is 
occasionally secondary to conjunctival conditions. It assumes two 
forms, ulcerative or superficial, and non-ulcerative or interstitial. The 
latter always causes opacity, varying directly according to the severity 
of the infiltration. Ulceration always results in scar formation, as 
do the higher grades of infiltration. Milder grades of the latter may be 
removed without leaving any serious visual defect. 

The microscopical changes in keratitis are swelling and degenera- 
tion of the corneal corpuscles, about which there may be some prolif- 
eration of these cells and an infiltration of a few leukocytes. At the 
margin of the cornea there is always vascular injection and very early 
appearance of new capillaries growing in the direction of the lesion. 

Infiltration may go on to suppuration and perforation. When ulcer- 
ations or suppurations perforate, there is an escape of aqueous and re- 
lease of pressure with forward dislocation of the iris or even of the lens. 
The iris may adhere to the edges of the rupture (anterior synechia), and 
the contact of the lens with the lesion in the cornea may cause anterior 
polar cataract. Perforation of an infected corneal lesion may lead to 
pus in the anterior chamber, hypopyon. Healing of deep corneal defects 
occurs by fibrous tissue, leaving opacities. In healing the cornea some- 
times is flattened instead of having its normal curvature, a facet being 
formed; again, a protrusion may occur where the newly formed tissue 
is not able to resist the intra-ocular pressure — staphyloma. Keratitis 
may lead to panophthalmitis. 

Interstitial Keratitis. — This condition, commonly due to general dis- 
eases like syphilis and gout, is characterized by the formation of opaque 
mottlings, or a complete ground-glass appearance of the cornea. It is 
caused by a cellular infiltrate without tendency to abscess formation. 
One variety, the marginal, is densest around the scleral insertion, 



THE EYE 



971 



and, another form, the vascular, shows a production of new blood- 
vessels (pannus) growing in from the periphery. The epithelium may 
be eroded or hypertrophic. 

Bullous keratitis is a condition in which crops of vesicles appear 
associated with considerable pain. Herpes of the cornea is of the same 
nature, but the vesicles are smaller and the cornea may be anesthetic; 
one variety is due to a disease of the fifth cranial nerve. Another con- 
dition associated with the disease of this nerve, with its consequent loss 
of sensibility of the cornea, is the so-called neuroparalytic keratitis, an 
ulcerative process limited to the cornea and prone to suppuration. 

Ulcerative keratitis may be secondary, or arise as the result of infil- 
tration in the cornea itself. The ulcers may be single or multiple. 




Fig. 450. — Perforating ulcer of the cornea with incarceration of iris (from a photomicro- 
graph) (de Schweinitz). 

In the simpler varieties there is a swelling, then denudation of the epi- 
thelium, shortly followed by a shallow ragged loss of substance of the 
cornea. There is only a pericorneal congestion and little tendency to 
pannus. 

Phlyctenular keratitis, associated with the similar disease of the 
conjunctiva, is characterized by the production of papules composed 
of lymphoid cells, which tend to soften and form ulcers which spread 
toward the corneal center, surrounded and followed by new blood- 
vessels. They heal from the margin, but opacity always results. 
Perforation or extension by continuity may occur. In healing of su- 
perficial ulcers of the eye epithelium grows out to cover the defect 
before the subjacent tissues heal. 



972 



A TEXT-BOOK OF PATHOLOGY 



Suppurative keratitis may be diffuse or localized. In either ease ul- 
ceration with perforation is likely to occur. Serpiginous ulcer, due 
frequently to the pneumococcus, is perhaps the most common va- 
riety. The ulcer spreads superficially rather than in depth, but per- 
foration is not uncommon. Discrete abscesses may occur in the cornea. 

Keratomalacia is an acute degenerative (fatty) change of the corneal 
epithelium, usually associated with inflammation, occurring in debili- 
tated children. Sluggish ulcers may arise. 

Ring abscess, or ulcer of the cornea, is merely peculiar in its circum- 
ferential spread. The whole cornea may slough off. 

Syphilis may appear as an acute or subacute infiltrative lesion, and 
gumma is known in this locality. 

Tuberculosis is usually secondary to adjacent tuberculosis, and 
appears as an infiltrative and sclerosing process. 

Leprosy appears as a nodular keratoconjunctivitis with a histology 
comparable to that of leprosy of the skin. 

Arcus senilis is a hyaline degeneration of the cornea in annular 
form near the periphery, but separated clearly from the sclera. It 
usually begins above and extends laterally. It is a pale gray band at 
first, but later becomes opaque, silvery, or gray white. It is said to be 
due to faulty nutrition when the circumferential vessels are diseased. 

Wounds of the cornea may be superficial, leading to simple destruc- 
tion of tissue, which is repaired without scar or followed by ulceration 
and opacities; or penetrating, in which case deeper structures are usually 
involved and the humors are infected or may escape. Wounds leading 
to ulceration if associated with extensive fibrous tissue repair may lead 
to pterygium or, rarely, to symblepharon. 

Tumors are exceedingly rare in the cornea. Papilloma and myo- 
fibroma have been reported. 

Cysts arise in the cornea under the same conditions as in the 
conjunctiva. 

The Anterior Chamber. — Inflammation of Descemet's membrane 
may arise by extension from inflammation of contiguous structures 
and presents the changes observed in other serous membranes. Pus 
(hypopyon) arises in the anterior chamber from any sort of infected 
corneal ulcer, wound, etc. 

SCLERA 

Episcleritis is an acute superficial hypertrophic and infiltrative 
inflammation of the exposed part of the sclera, characterized by low 
dark red granulations or papules, consisting of lymphoid and poly- 
nuclear cells and accompanied by small hemorrhages and edema. This 
heals without cicatrization. The conjunctiva is movable over these 
excrescences and is injected. 

Scleritis is a deep, diffuse, infiltrative, overproductive inflammation 
of the sclera, usually of the exposed part, arising, after exposure, in 
rheumatic, gouty, and syphilitic individuals. It assumes a nodular form 
associated with hemorrhage and edema. Healing occurs by cicatriza- 



THE EYE, 



973 



tion which leads to thinning and weakening, in consequence of which 
scleral staphyloma results. One syphilitic form grows as a pericorneal 
band, consisting, microscopically, of young granulation tissue. 

The importance of injury to the sclera depends upon whether or 
not a puncture has been effected with disturbance of relation of the 
various intra-ocular structures, and the introduction of germs. In 
the presence of these unfavorable factors healing will take place by 
scar tissue of course, and lead to destruction of the ciliary body or lens 
and to weakness of the ball membranes. Tension by scar tissue upon 
the ciliary body may cause increased intra-ocular pressure. The sclera 
may be ruptured by a blow upon the eye. 

Tuberculosis, syphilis, tumors, and cysts are exceedingly rare in the 
sclera. 

THE CRYSTALLINE LENS 

Congenital abnormalities of the lens take the forms of cataract, 
false position, or abnormal curvature, or it may be involved in a colo- 
boma. Opacity of the lens (cataract) is the principal acquired patho- 
logical change. This is due to hyperplasia of the capsular epithelium 
or degeneration of the internal fibers. When due to the former it is 
called capsular, when to the latter, lenticular, cataract. 

Capsular cataract is usually encountered near the middle of the 
anterior surface, and is ascribed to some form of insult from the front 
of the eye, in response to which the lens capsule proliferates, the epi- 
thelium first becoming reduplicated, then stratified. An opaque degen- 
eration of the epithelial fibers accompanies or follows the capsular 
change. Posterior capsular cataract is either congenital, due to the 
remains of the hyaloid artery, or secondary, due to long-standing dis- 
ease of the posterior segment of the eyeball, especially in the choroid. 

Lenticular cataract is a degeneration involving in part or wholly the 
fibrillar structure of the lens, rendering it opaque. The traumatic 
variety is understood, but those due to constitutional disease, inflam- 
mations in contiguous structures, or senility are vague in etiology. 
It is said that the essential feature in all cataracts is an altered tension 
in the capsule and nucleus, which permits invasion of the fibrous struc- 
ture by the aqueous humor. The first change seems to be a shrinking 
of the lens, shortly followed by swelling as the fluid penetrates. This 
fluid collects in globular masses as do also the remains of degenerated 
fibers. The capsule may be in natural condition or proliferating. 
The interior of the lens may soften to a liquid mass in which the nucleus 
may float or sink (Morgagnian cataract). After the lens has softened 
some shrinking is noticeable, due probably to beginning absorption. 

There are various forms of cataract recognized by ophthalmologists, 
depending upon the arrangement of the opaque areas. Their path- 
ology is essentially the same however. 

A cataract of the lens fiber may arise from any trauma which so 
affects the capsule as to permit the invasion of the aqueous. It may 
be a part of or accompanying an inflammation of contiguous tissues. 



974 



A TEXT-BOOK OF PATHOLOGY 



Dislocation, or luxation, of the lens may occur from trauma or from 
disease. In the former case the lens may penetrate the vitreous or 
anterior chamber, or, by rupture of the iris and of the insertion of the 
cornea, to a position under the conjunctiva. Pathological luxation may 
be due to degeneration of its suspensory ligament, or in atrophy after 
cataract. 

THE VITREOUS HUMOR 

Hemorrhage into the vitreous arises only from injury or disease of 
surrounding tissues. In the latter it may arise from simple inflam- 
mation, but more often it is the result of dyscrasia or diseased vessel 
walls. 

Chemical changes in the vitreous are due to disease of the choroid 
or retina. They comprise infiltrates of phosphates, fat, cholesterol, or 
osseous matter. The last supervenes sometimes upon overgrowth of 
connective tissue from chronic retinitis or choroiditis. Opacities usually 
arise as a result of these chemical changes. Degenerative changes take 
the form of fibrillation and liquefaction. The mass soon shrinks by 
loss of fluid. 

Inflammation is secondary to disease in retina, choroid, and ciliary 
body. Microscopically, there is mild leukocytic infiltration with coarse 
fibrillation. 

The vitreous may escape in punctured wounds, permitting hemor- 
rhage and detachment of the retina. Foreign bodies, filaria, and cysti- 
cercus cysts have been found in the vitreous. 

THE IRIS 

Congenital abnormalities of the iris take many forms, affecting 
its continuity or pigmentation. Affections of the continuity embrace 
obstruction of the pupil by persistence of the anterior vascular capsule 
of the lens which occupies the pupillary space in the embryo; dy scoria, 
irregularity of the pupil and distortion of the iris muscles; polycoria, 
the existence of several openings in the iris; cor ectopia, or incorrect 
position and shape of the pupil; and coloboma, taking the form of a 
linear defect extending from the pupil even to the ciliary body. Occa- 
sionally the coloboma may be very extensive or the iris absent entirely. 
This is aniridia. 

Abnormalities of pigmentation consist of its absence, albinism; or 
excess, melanosis; or of mixtures of colors, especially eyes of different 
colors, known as heterochromia. 

Atrophy of the iris occurs as the result of recurrent acute attacks of 
inflammation, or by interference with its blood-supply, as from prolonged 
intra-ocular pressure or traction upon the ciliary body. It may occur 
as a result of senility. The pathological changes embrace fibrous and 
hyaline deposits particularly in and around the blood walls, irregularity 
or loss of pigment, and at times a hypertrophy of the endothelium 
reflected from Descemet's membrane, a sort of replacement hyperplasia. 



THE EYE 



975 



Hyperemia of the uveal tract may be an early stage of inflam- 
mation, or the result of disease in adjacent tissues. 
Anemia is merely a part of general anemia. 

Inflammations of the iris may be acute or chronic, but are always 
exudative in character. The acute may be serous, purulent, simple 
plastic, or combinations of these. 

In serous iritis the membrane is swollen, congested, and there is a 
watery exudate in the anterior chamber which may or may not contain 
shreds of lymph. This condition is prone to spread to the ciliary body 
and choroid, thence to the vitreous, which may develop opacities. 

In plastic iritis, the more frequent form, and usually associated with 
inflammation in the rest of the uveal tract, the process is of greater in- 
tensity, fibrinous exudate appears, and tabs of lymph are found upon the 
iris and Descemet's membrane; synechia maybe found. Synechia may 
attach the iris to the anterior surface of the lens around the pupillary 
opening (annular synchia), or the whole iris may become fast (total pos- 
terior synechia). The exudate is at times extensive enough to span the 
pupil. Under these conditions of synechia and closure of the pupil the 
iris becomes fixed, and outflow of the aqueous humor from the ciliary 
processes and posterior chamber through the pupil into the anterior 
chamber is hindered. Then increased intra-ocular pressure arises. 
This inflammation practically always involves also the rest of the 
uveal tract. 

Purulent iritis may succeed upon the foregoing, and in its spread and 
results differs little from it except that it is more rapid and extensive. 
Pus in the anterior chamber (hypopyon) is an almost constant feature. 

The pathogenesis of these forms of iritis is essentially the same. 
The process begins as a congestion and infiltration, usually in the loose 
layer of the iris, causing hyperplasia or rupture of the endothelium, 
with a collection of exudate upon this surface that may extend back- 
ward to the ciliary body and choroid. There is injection of the peri- 
corneal zone. The causes of iritis, aside from mutilating injury with 
infection, syphilis, rheumatism, and gout, are obscure. These three 
last usually cause subacute plastic iritis. Iritis when chronic is com- 
monly syphilitic, and is characterized by endo- and peri-arteritis and 
accumulations of round and epithelioid cells, the infiltrate frequently 
showing hyaline change. 

Tuberculosis of the iris is probably always secondary, and appears 
as a diffuse seroplastic thickening, as miliary tubercles, or as a large 
caseous mass. The miliary form appears as disseminated yellow dots 
which soon coalesce and extend to the ciliary body. Caseous tubercu- 
losis takes the form of a rapidly growing tumor-like mass composed of 
fused tubercles, which tends to grow outward and rupture the eyeball. 
Tuberculosis of the iris is usually unilateral. It is a disease of 
youth. 

Syphilis of the iris appears as a secondary or tertiary manifestation 
in the form of an acute seroplastic inflammation, or as gumma. The 
former consists of specific arteritis and peri-arteritis with added round- 



976 



A TEXT-BOOK OF PATHOLOGY 



cell infiltration. Gummata are commonly found on the pupillary or 
ciliary borders and do not differ from gummata elsewhere. 

Tumors. — Primary tumors are exceedingly rare, melanosarcoma 
being the principal variety. Occasionally angiomata are seen in the 
form of neevi, which may be pigmented and give rise to sarcoma. It 
is said that endo- and perithelioma may arise from them. 

Cysts. — Parasitic and dermoid cysts have been reported. Some- 
times cysts arise from bits of epithelium which have been forced into 
the iris by violence, as is the case with the cornea. 

THE CILIARY BODY 

Atrophy of the ciliary body is secondary to inflammation, and 
occurs in old age. The processes become flattened and the secretory 
functions disturbed. 

Inflammation, or cyclitis, is seldom a solitary process, usually 
being a part of or secondary to iritis,, as iridocyclitis. The process is 
commonly plastic, although it may be purulent. The condition affects 
the substance of the body and the exposed part within the posterior 
chamber. The organization of the fibrinous exudate causes the anterior 




Kg. 451. — Traumatic iridocyclitis. Diffuse infiltration of the iris and ciliary body 

(de Schweinitz). 

walls of the posterior chamber to adhere to the lens (synechia), and the 
inflammatory process invades the lens capsule and vitreous. In severe 
cases the last-named structures are infiltrated, degenerated, and con- 
tain opacities. The lens may be dislocated and the uveal tract drawn 
inward from the sclera by traction of fibrous tissue. The retina may 



THE EYE 



977 



be detached. These lesions cause such disturbance of nutrition that the 
bulb begins to soften and -phthisis bulbi results. 

Tuberculosis assumes the same forms as in the iris. 

Syphilis of the ciliary body alone is rare, but gummata are reported. 

Tumors. — Glioma is the commonest tumor and arises from the 
retinal segment of the ciliary body. Sarcoma, either simple or melanotic, 
sometimes occurs. 

Cysts are very common, and are said to be due to epithelial inclu- 
sions. 

THE CHOROID 

Hemorrhage in the choroid is common because of the high vascu- 
larity of the membrane. Minute hemorrhages occur under various 
conditions, but their exact cause is not known. They may lead to 
atrophy of the membrane. Large hemorrhage is due to trauma. 

Atrophy of the choroid may be due to hemorrhage, inflammation, 
or nutritional disturbances. Sometimes collections of so-called "colloid" 
matter are found among the elastic fibers. 

Wounds and ruptures are serious because they usually cause sepa- 
ration of the retina and escape of the vitreous to a position beneath 
the sclera. The' choroid may be detached from the sclera by hemor- 
rhage or exudation. 

Inflammation. — In considering inflammation of the choroid it is 
difficult to separate this membrane from the ciliary body and iris in 
front, and the retina within. Disease arising in any one of these parts 
may extend to the others (uveitis), and when all these contiguous struc- 
tures are invaded the chances of full repair are small. The bulb and 
its surrounding tissues are swollen and infiltrated. 

Choroiditis is an exudative process, serous, plastic, or suppura- 
tive in type. Its causes, aside from involvement by extension, are 
auto-intoxication, gout, rheumatism, syphilis, tuberculosis, and, occa- 
sionally, the acute infections, like erysipelas or typhoid fever. It is 
commonly associated with inflammation of the retina, although one 
coat may be affected without the other. 

Serous choroiditis appears suddenly, with swelling of the membrane 
and opacity of the vitreous. 

Purulent choroiditis follows the same course, but the exudate as a 
cloudy mass soon infiltrates the ciliary body and iris, and collects in the 
anterior chamber. The vitreous and retina are shortly involved. 

Chronic choroiditis may be diffuse or disseminated. The dissemi- 
nated forms occasion rounded irregular patches of infiltration over the 
fundus which spread and coalesce; the retina over them becomes hazy. 
These infiltrations may dissolve, leaving in their place pale areas of 
fibrosis which soon take up pigment. These areas may spread by de- 
generation and connective-tissue growth even after the active inflam- 
mation has ceased. They may have calcareous deposits in them. 
Retinal atrophy over them may result. 

Diffuse choroiditis is characterized by the appearance of large yellow 

62 



978 



A TEXT-BOOK OF PATHOLOGY 



coalescing plaques of exudate over which the retina is edematous. 
Atrophy of vessels and retinal elements, even of the optic nerve, 
results. 

In acute and chronic cases of choroiditis contiguous structures are 
usually involved. After choroiditis, especially of recurrent nature, the 
internal surface tends to form granulation tissue with exuberant 
growth into the vitreous, with, first, hypertrophy, then atrophy, of the 
retina. The type of infiltrating cell in both acute and chronic in- 
flammation, except, of course, the suppurative, is that of the lympho- 
cyte series. 

Tuberculosis of the choroid is commonly of the miliary variety, 
but a diffuse infiltrative or large caseous tuberculosis is reported. 
Miliary lesions seem to occur mostly on the outer surface, while the in- 
filtrative or caseous processes prefer the inner layers. 

Syphilis usually causes a serous or plastic choroiditis, but the cho- 
roid is seldom involved without the retina. 

Tumors. — Sarcoma is the most important, and is usually of the 
melanotic variety, a very malignant growth giving many metastases. 
Among the varieties met with there may be melanotic, simple, alveolar, 
or angiosarcoma, and, related to the last, peri- and endothelioma. 

Carcinoma occurs only as a secondary growth, as does glioma. 

THE RETINA 

Anemia is due to general anemia or obstruction of the central retinal 
artery by thrombosis or sclerosis. Fatty degeneration may follow it. 
Blindness results at once from any sudden stoppage of the artery, such 
as from embolism or spasm. 

Active hyperemia is due to long-continued irritation, inflammation, 
or high arterial tension. 

Passive hyperemia is due to: (a) conditions in the eye itself, glau- 
coma, choked disk; (b) conditions in the orbit, cellulitis, tumors; and 
(c) conditions away from the eye, heart disease, cranial growth, sinus 
thrombosis. Grossly, there is lengthening, distention, and tortuosity 
of the«arteries and veins of the eye-ground. Hemorrhage from such 
vessels may occur. 

Hemorrhage. — Retinal hemorrhage occurs from hyperemia, trauma, 
and vascular disease; in the last are included thrombosis, angiosclerosis, 
and acute angiitis. The diseases in which hemorrhage is apt to occur 
are nephritis, diabetes, gout, rheumatism, general arteriosclerosis, 
anemia, leukemia, purpura, acute infections, and certain poisonings. 
The hemorrhages appear as radiating red splotches in the neurofibrillar 
layer, or they may take the form of irregular extravasations into or 
beneath the retina, or even into the vitreous. The blood may be ab- 
sorbed and leave areas which undergo fatty degeneration, spots of blood- 
pigment remaining. Larger hemorrhages may leave an organized clot. 

Atrophy is a consequence of prolonged inflammation leading to 
disturbance of nutrition, or is a senile change. A similar change in the 



THE EYE 



979 



choroid is usually found. The microscopical alteration consists in a 
shrinkage of the cellular layer with separation of the rods and cones. 
The cells and fibers show some fatty metamorphosis, and fibrous tissue 
increases, particularly between the retina and choroid. Pigment is 
decreased. 

Detachment of the retina is the separation of the membrane by 
splitting between the pigmented layer and that of rods and cones. It 
is a serious progressive condition due to some disease or injury to the 
eye. The membrane remains uncertainly suspended in the vitreous 
chamber. 

Inflammation. — As is the case in inflammation elsewhere in the 
inner eye, retinitis is infiltrative and exudative. The simplest form is 
little more than a marked edema of the retina, but deserves to be placed 
among the inflammations because there may be cellular infiltration 
associated with edema. This exudate may undergo some form of re- 
generation. Serous retinitis may proceed to 

Purulent retinitis, a condition usually due to perforating wounds, 
but which also arises metastatically. The process is a swelling with 
infiltration of pus throughout the retina, which is soon detached, and 
then the vitreous and anterior segment of the eye are attacked. Hem- 
orrhage frequently occurs. Panophthalmitis always supervenes. 

Albuminuric retinitis, a characteristic change in nephritis, is really 
a neuroretinitis. There is swelling, reddening, and obscurity of the 
nerve-head, around which spot are radiating linear hemorrhages and 
pale anemic coalescing areas, which are hyaline or fatty degenerations. 
The vessels are distended and tortuous. The minute changes are those 
of chronic retinitis and marked sclerosis of the vessels. Degeneration 
of the nerve-fibers also occurs. 

Diabetic retinitis is a hemorrhagic process. The optic nerve-head 
is less apt to be swollen, and the retina in general is more normal 
in appearance than in the preceding, save for irregular or linear hem- 
orrhages. There is, nevertheless, a mild chronic retinitis. 

Chronic retinitis assumes many forms for the clinician, but the his- 
tological changes are essentially the same in all. There is cellular infil- 
tration of the vitreous layers with fibrous tissue growth inward from 
the parts near the choroid. In the infiltrate are endothelial cells of 
obscure origin, probably from the adventitia of blood-vessels, which tis- 
sue is actively hyperplastic. Giant cells are common. In the organiza- 
tion of chronic retinitis the choroid may become adherent and the 
inner retinal fibrillary layers become wrinkled and proliferative, even to 
the extent of showing granulation tissue. The fibrous layer of the retina 
may also undergo liquefaction or fatty degeneration. In diffuse retinitis 
these changes are more or less evenly distributed, but there is a dis- 
seminated form in which patches of chronic inflammation occur, and 
in this variety the internal overgrowth of tissue is commonest. 

Retinitis pigmentosa, or pigmentary degeneration of the retina, is a 
chronic progressive atrophic process beginning at the equator or ante- 
rior thereto and proceeding backward, characterized by the deposit 



980 



A TEXT-BOOK OF PATHOLOGY 



of black pigment in splotches with extensive radiations. The retina 
about the optic disk is the last part to be affected. Under the micro- 
scope there is found obliterating endarteritis with hyaline degeneration 

and deposit of pigment in the vessel walls, 
and disappearance of the normal pigment. 

Tuberculosis of the retina is usually 
secondary to adjacent tuberculosis. It is of 
the miliary variety. 

Syphilis of the retina in an acute or 
chronic form assumes the vascular prolifera- 
tive character peculiar to this infection. 

Tumors. — Glioma is the only primary 
tumor certainly arising in the retina. It is 
commonly met with in children, and may 
be due to congenital defect. It is a pro- 
gressive tumor usually growing forward 
through the eyeball and presenting a slough- 
ing cauliflower-like mass externally. This 
tumor is prone to give metastasis to bones 
and glands; is very cellular and rich in blood-vessels; and most often 
originates from the inner nuclear layer of the retina. 

Angiomata and fibromata are reported, but their origin is not certain. 




Fig. 452. — Glioma of retina 
(patient in the University Hos- 
pital) (de Schweinitz). 



SYMPATHETIC OPHTHALMITIS 

When an eye has been injured, with the result that a uveitis arises, 
the other and uninjured eye may be affected in sympathy. This sym- 
pathetic ophthalmitis takes the form of a subacute remitting or recurrent 
plastic or serofibrinous uveitis, upon which a panophthalmitis may 
supervene. Posterior synechia, corneal opacity, staphyloma, or glau- 
coma may ensue. Sympathetic ophthalmia may follow perforating 
wounds in the ciliary region, especially if a foreign body be retained; 
old retinitis with calcification acting as a foreign body; long-standing 
iridocyclitis; luxation of lens; pressure of an artificial eye; or irritation 
of the optic nerve stump by fibrous tissue after enucleation. The defi- 
nite cause is not known, but is variously ascribed to some special 
micro-organism and reflex nerve irritation. It has lately been sug- 
gested that there is very commonly an underlying taint of syphilis or 
tuberculosis, a proposition strengthened by the beneficial effects, in 
some cases, of measures directed against these diseases. 

GLAUCOMA 

The normal intra-ocular tension is maintained by the proper secre- 
tion and escape of the aqueous humor. If its escape be hindered, 
pressure rises and glaucoma results. The condition may be considered 
primary when no demonstrable cause exists, and secondary when 
traumatic or inflammatory disease of the bulb has preceded it. The 



THE EYE 



981 



secondary form is due to synechia? obstructing the aqueous current be- 
tween the posterior and anterior chambers, to inflammatory lesions 
of the ciliary body, or to obstruction at the iridocorneal juncture, in- 
cluding the spaces of Fontana or Schlemm's canal. Such lesions either 
render the aqueous humor too viscid to filter easily or hinder absorption. 
Primary glaucoma may arise in the apparently healthy eye. Arterial 
disease seems to favor its development. The eye in acute glaucoma is 
swollen, cloudy, injected, lusterless, and the pupil shows a green appear- 




Fig. 453. — Section of optic nerve-head containing a deep glaucomatous excavation, 
the so-called kettle-shaped excavation: r, Retina; ch, choroid; s, sclera; c, cup or excava- 
tion, pushing back lamina cribrosa (de Schweinitz). 

ance. Hemorrhages sometimes occur. In chronic glaucoma there is 
progressively increasing hardness of the eye, atrophy of the retina, 
and "cupping of the disk," a condition due to posterior staphylomatous 
protrusion at the lamina cribrosa with degeneration of the optic nerve. 



THE OPTIC NERVE 

Hyperemia is found under the conditions given for Hyperemia of 
the Retina. 

Inflammation. — Inflammations affect either the retinal portion of 
the nerve (papillitis) or the extra- or retrobulbar portions. The causes 
of this disease are metastatic in infections, or involvement by continuity 
from the retina, meninges, or orbital tissue. There is also a congestive 
form in cases of vascular obstruction, such as by intracranial new 
growths or increase in the quantity and pressure of the cerebrospinal 
fluid; in this case there is simple edema and hyperemia. 

Papillitis, papillo-edema, or choked disk, is a swelling of the retinal 
end of the optic nerve with indistinctness of its outlines. There may 
be small hemorrhages, sometimes in radial linear arrangement. The 



982 A TEXT-BOOK OP PATHOLOGY 

nerve-head is turbid when infiltration is marked, and minute examina- 
tion reveals edema, round-cell infiltration, and granular degeneration 
of the nerve-fibers. In inflammation of the trunk of the nerve infiltra- 
tion is the same, but one finds proliferation of the endothelial lining of 
the intraneural spaces and degeneration and atrophy of the nerve- 
fibers. The form of papillitis dependent upon increased intracranial 
pressure partakes chiefly of the nature of atrophy, although both this 
and the atrophies of the nerve-head which accompany constitutional 
disease usually pass through a low inflammatory process similar to that 
just given. Atrophy of the optic nerve from conditions not arising 
within the eyeball may be due to pressure by lesions in the orbital 





Fig. 454. — Ophthalmoscopical picture of papillitis and semidiagrammatical representation 
of a longitudinal section of the nerve-head (de Schweinitz). 

tissues, or from diseases like paresis and tabes, and poisoning from 
quinin or tobacco. The degenerations and atrophies depend upon the 
production of areas of ischemia and upon selective action of poisons 
for certain nerve elements. 

Tuberculosis affects the optic nerve as miliary tubercles in the 
sheath. 

Syphilis takes the form of gumma or neuritis. 

Tumors. — The primary tumors of the nerve are divided into the 
intra- and extradural forms. The former comprise myxoma, fibroma, 
psammoma, endothelioma, and sarcoma. Extradural tumors are 
fibroma, endothelioma, and sarcoma. 



THE EYE 



983 



THE ORBIT 

Abnormalities of Position of the Bulb. — The most important 
condition under this heading is exophthalmos or proptosis. This is due 
to swelling of the areolar supporting tissue within the orbit, as from 
inflammation, venous congestion, hemorrhage, or tumors. The results 
are stretching of the muscles and consequent incorrect position of the 
eye in the visual axis; stretching of the optic nerve if the protrusion of the 
ball is greater than the slight amount of slack that the curve in the nerve 
can give, upon which optic neuritis may ensue. If the lids be unable to 
close there may arise conjunctivitis and keratitis with ulceration due to 
the dryness and lack of protection from dust. In exophthalmic goiter 
the proptosis is variously ascribed to a spasm of the muscle of Miiller, 
orbital hyperemia, and irritation of the sympathetics. In postorbital 
aneurysmal varices there may be a pulsating proptosis. 

Enophthalmos is sinking in of the bulb when the posterior orbital 
tissues are absorbed, or from a fracture of the skull involving the orbit. 

Inflammations affect the orbital tissue as cellulitis or abscess, and 
arise from injury, extension, or metastasis. Periostitis of the orbital 
bones may arise under the usual causes for this disease. 

Tumors arise from the optic nerve, as above; from the perios- 
teum, fibromata, exostoses, and chloroma; from the ball-supporting 
tissue, angioma, lymphoma, and sarcoma, including endothelioma. 
Epithelioma may arise in the lids. 

THE LIDS 

Edema may be traumatic or accompany ocular inflammation. 
It occurs in angioneurotic edema and exophthalmic goiter. 

Ptosis is incomplete elevation of the upper lid, and may be due to 
congenital absence of muscle power, or to muscle impairment by palsies 
of the third cranial nerve. 

Inflammation. — Blepharitis, inflammation of the lids, may be a 
simple catarrhal process, but the more chronic cases assume the form 
of a productive conjunctivitis and dermatitis. By organization and 
fibrosis in severe cases the ciliary margin is destroyed and the tear 
puncta either obstructed or rendered useless by thickening or eversion 
of the lid. A chronic conjunctivitis and keratitis may ensue. 

Stye, or hordeolum, is a small abscess in a hair-follicle. A chronic 
granuloma of the Meibomian glands with histology like a tubercle, but 
not of tuberculous nature, is called chalazion. 

Tumors. — Epithelioma, carcinoma, and, occasionally, sarcoma have 
been seen. Of the benign tumors, papilloma, fibroma, and adenoma are 
reported. The glandular tumors arise from sebaceous and Meibomian 
glands. 



CHAPTER XVI 



THE EAR 



ANATOMY 



The external ear consists of the auricle and external auditory canal. 
The former is composed of skin and yellow elastic cartilage. The 
canal is cartilaginous in the outer part, lies within the temporal bone 
for the inner part, and is lined with skin containing sudoriferous and 
sebaceous glands which secrete cerumen. 

The tympanic membrane separates the external and middle ears. 
Externally, this curtain is covered by skin, internally, by a mucous 
membrane between which layers there is a fibrous layer into which the 
malleus is inserted. At the superior portion of the tympanic membrane 
there is an umbrella-shaped section of thinner tissue, Shrapnell's mem- 
brane, supported on either side by strong fibrous folds. Within the 



Elevation of tympanomastoid semicircular 
canal in aditus ad antrum 

Oval window 
Canal for tensor tympani muscle 



Osseous Eusta- 
chian tube 
Facial canal at 
point of turn- 
ing backward 
Carotid canal 



Mastoid antrum 




Annulus tympanicus 

External auditory meatus' 
Glenoid fo; 



Fig. 455. — Section of temporal bone in plane of mastoid antrum. Aditus, tympanum, and 
Eustachian tube, showing direct connection of all these spaces (Barnhill and Wales). 

membrane, situated in the petrous portion of the temporal bone, is the 
tympanum, or middle ear. Behind it lies the mastoid portion of the 
temporal bone with the cells of which there is a communication; be- 
low it is the roof of the jugular fossa. From the anterior part of the 
floor of the tympanum the Eustachian tube passes downward, for- 
ward, and inward to the pharynx, through the canalis musculo- 
tubularis, which also carries the tensor tympani muscle. There is a 
natural isthmus of the tube 2.5 cm. from the pharyngeal ostium. The 
Eustachian tube is lined by ciliated epithelium. Suspended in the 
tympanum, the chain of ossicles is inserted externally into the external 
tympanic membrane, internally into the oval window. The cavity is 
lined by cuboidal epithelium. The internal ear consists of a vestibule 

984 



THE EAR 



985 



into which the oval window opens, semicircular canals, and cochlea; 
this is also called the labyrinth, and consists of a membranous part 
lying in a bony cavity of the same shape and arrangement. The semi- 
circular canals are disposed in the three geometric planes, and the 
lining is mucous membrane rich in branches of the auditory nerve 
and covered with ciliated epithelium. The cochlea, a conical spiral 
body, lies before the vestibule and contains the organ of Corti, the 
special end-organ of hearing. The auditory, or eighth cranial nerve, 
passes into the ear by the internal auditory meatus and divides into 
branches which go to the cochlea, vestibulum, and semicircular canals. 

CONGENITAL DEFECTS 

The defects in formation of the ear are of little pathological impor- 
tance, aside from absence or atresia of the meatus, absence of the exter- 
nal tympanic membrane or Eustachian tube, and hypoplasia of the 
functional structures like the ossicles and internal ear. Whole sections 
are sometimes missing. 

THE EXTERNAL EAR 

Hyperemia and hemorrhage are of slight importance, and are due to 
inflammation or injury. 

Hematoma auris occurs as a diffuse hemorrhagic extravasation be- 
tween the cartilage and its covering, and is due to trauma or certain 
dyscrasias. It occurs frequently in the insane, commonly on the left 
side, a fact which suggests that trauma may be its cause. Fibrosis, or 
degeneration of the cartilage, may result. 

Deposits of uratic or calcium salts are sometimes seen in the car- 
tilage or its covering. Within the auditory canal one frequently 
sees collections of cerumen and desquamated epithelium, even to the 
extent of forming hard tenacious masses. This is of little importance 
unless of long standing, under which conditions the skin may show der- 
matitic changes, and that portion over the drum may become eroded. 
Foreign bodies are frequently found in the external auditory canal. 
They may cause inflammation, but are more important because of the 
reflex nervous phenomena they occasion. Flies may lay their eggs 
and maggots grow within the canal. 

Inflammations. — Perichondritis is an exudative process in which 
the perichondrium is lifted from the cartilage. It may be localized or 
diffuse. Degenerations of the cartilage may ensue. 

Purulent auriculitis may follow the last, but is more apt to assume 
the form of boil or abscess, beginning in a sweat or sebaceous gland. 

The more diffuse non-purulent inflammations of the outer ear 
usually assume the form of a dermatitis of the canal, which may be of 
simple infiltrative or pseudomembranous nature. Suppurative proc- 
esses do occur, but usually after trauma. 

Frost-bite of the auricle presents an edematous or bloody swelling 
which may proceed to ulceration or gangrene. 



986 



A TEXT-BOOK OF PATHOLOGY 



Tuberculosis occurs as nodular fibrous tubercles without tendency to 
coalesce, but they do ulcerate late in the disease. 

Syphilis occurs as primary lesions, secondary ulcerations in the 
canal, or gummata. 

Mycosis. — Moulds of the genera Aspergillus, Mucor, Oidium, and 
others grow in the external canal when moisture and a mild dermatitis 
make favorable soil for their development. The growth may be super- 
ficial, or may penetrate the skin or even to the middle ear. 

THE TYMPANIC MEMBRANE 

Hemorrhage occurs through traumatism, or spontaneously in 
certain general infections, or in hemophilia, scurvy, and purpura. 

Atrophy is the result of long-continued irritation by cerumen, 
concretions, inflammation, or by increased intra-aural tension by morbid 
collections. The whole membrane or only its fibrous layer is affected. 

LP 

Fig. 456. — Normal drum membrane as Fig. 457. — Bulging drum-head with be- 

viewed through a speculum by reflected ginning necrosis at the point of greatest 
light (Barnhill and Wales). pressure (Barnhill and Wales). 

Rupture occurs by direct or indirect injury. Those due to indirect 
force, blows, explosions, etc., are usually in the anterior or superior 
parts. The drum may be perforated from within outward by inflam- 
mation in the tympanum, or by pressure necrosis; in the first case the 
membrane itself may be involved. Healing is accomplished by cica- 
trization, in which the fibrous layer may not be replaced and in which 
calcification not infrequently appears. 

Inflammation. — Acute inflammation is either an infiltrative or 
catarrhal condition. The membrane is swollen, opaque, and may 
show small dots of greater accumulation of the exudate. It is due 
to extension from other inflammations or direct injury. 

Chronic inflammation is secondary to acute, or to prolonged or 
repeated otitis media. There is diffuse or irregular fibrous thickening 
and nodular granulation tissue. 

Tuberculosis occurs as miliary lesions or caseous masses. 

Syphilis takes the form of mucous patches or gummata. 

TUMORS OF THE EXTERNAL EAR 

Polypi are the commonest masses in this situation, and are usually 
due to overgrowth after inflammation. Various degenerations occur in 
them. Warts have been seen in the canal or on the drum-head. Ecchon- 
droses or exostoses grow from the perichondrium or periosteum, and may 




THE EAR 



987 



be sessile or pedunculated. A curious and not uncommon form is annu- 
lar; it often follows prolonged inflammation and is said to be due at 
times to too frequent cold bathing. 

True neoplasms of this area embrace fibroma, osteoma, chondroma, 
sarcoma, and carcinoma. Various angiomata are known. 

Upon the inner surface of the tympanic membrane cholesteatoma 
has been found. 

Sebaceous and dermoid cysts occur along the canal. 

THE MIDDLE EAR 

Hemorrhage is due to acute inflammation, trauma, caries of bone in- 
volving vascular channels, and it may occur spontaneously in nephritis. 

Passive hyperemia occurs in heart and lung disease, or pressure 
upon the jugular vein. 

Inflammation, or Otitis Media. — This disease process appears in 
acute and chronic types, and assumes a catarrhal, purulent, or fibrosing 
form. The etiology must consider the three ways in which the tym- 




Fig. 458. — Section of drum membrane: case of chronic otitis media suppurativa (prepared 
by Dr. H. C. Low) (Barnhill and Wales). 



panum can be infected. Extension from the pharynx and retro- 
pharyngeal tissue occurs through the Eustachian tube from various 
inflammatory foci. Bacteria may be forced up the canal by douch- 
ing or sneezing. Adenoids favor the collection of microbes near the 
tube openings in the pharynx (see Eustachian Tube). The cavity may 
be infected through the tympanum by injury or extension, while in the 
infectious diseases otitis media may be caused by germs brought in the 
blood-stream. Staphylococci, streptococci, and pneumococci are the 
commonest pus formers, but a single kind of organism is seldom present. 



988 



A TEXT-BOOK OF PATHOLOGY 



Catarrhal otitis media, in its acute form, produces a reddened, 
swollen, and infiltrated mucosa, and a turbid mucous exudate. The 
drum is congested and bulges. In the chronic form, either as a successor 
of the acute, or arising as a result of repeated irritations in rheumatic 
and gouty subjects, the mucosa is irregularly thickened and may show 
exuberant fibrous and epithelial granulations. The drum-head is prac- 
tically always stiffened and the ossicles limited in their movements. 

Purulent Otitis Media. — The acute purulent variety is commonly 
secondary to the catarrhal and there is really no sharp line between 
the two. The exudate becomes purulent, the infiltrate involves the 
drum-head, which softens and may slough, and the ossicles loosen or 
may be necrosed in the severe cases. Extension may take place through 
the petrososquamosal suture to the meninges or sinuses when the 
mucosa is ulcerated, or it may burrow to the external surface. The 
mastoid cells are practically always somewhat involved in otitis media, 
and when the inflammation is especially severe or protracted necrosis 
of the mastoid bone and septicemia are apt to occur. 

Chronic purulent middle-ear inflammation is a sequel of repeated 
acute attacks. The mucosa is considerably thickened by round and 
polynuclear cell infiltration and subepithelial granulation tissue. The 
cavity is filled with pus and blood, which, when the drainage is poor, 
may become inspissated. The tympanic membrane is usually perforated 
and its margins show granulation tissue. The bony casement of the 
tympanum is attacked by necrosis which may penetrate into the inner 
ear with extensive necrosis. The ossicles are at first loosened, then 
become necrotic. The penultimate stage is an enlargement due to the 
necrosis, while the last phase is one of total necrosis and extension to 
the skull, meninges, sinuses, or mastoid cells in the unfavorable cases, 
and fibrosis with bony overgrowth, middle-ear exostoses, in the more 
favorable ones. The cavity decreases in size in the last instance. 

In addition to the above chronic otitides there are varieties of 
fibrotic change of the soft parts within the tympanum which may be 
classed as inflammations because they are progressive, although unat- 
tended with much swelling, congestion, or infiltration. These changes 
may follow acute inflammation, but may also arise insidiously. One 
form is the polypoid proliferative variety, in which the fungoid masses 
are covered with cylindrical or ciliated epithelium. Adhesive otitis is 
due to the bridging of the cavity by bands of hyperplastic fibrous 
tissue. The bands sometimes cut off sections of the cavity, in which 
fluid collects, the cystic variety. Sclerotic otitis is an atrophic variety 
with interstitial induration, stiffening or ankylosis of the bone chain, 
periostitis, or exostosis in cases of long duration. 

Tuberculosis of the tympanum takes the form of an infiltrative 
ulcerative caseous lesion which follows the pathological course outlined 
for chronic purulent otitis media. It is always secondary. 

Syphilis appears in the tympanum as an acute or chronic inflam- 
mation in the secondary or tertiary stages. 

Tumors. — Polypi, the result of inflammation, are the commonest 



THE EAR 



989 



new growths. They may attain considerable size and protrude exter- 
nally. They are covered with epithelium which may show any form of 
metaplasia. Histologically, such masses present angiomatous, myxo- 
matous, fibromatous, or adenomatous characters. 

Malignant new growths are uncommon, but sarcoma and carci- 
noma are the most frequent. 

Cholesteatoma. — In some cases of chronic purulent otitis media 
there arises a mass made up of squamous epithelium and cheesy mat- 
ter. It is probably the result of metaplasia of the normal columnar 
epithelium into flat cells, which assume a lamellated arrangement. 
This so-called cholesteatoma is looked upon by most pathologists as 
due to prolonged irritation and not as a neoplasm. 

THE EUSTACHIAN TUBE 

Inflammation, usually of the catarrhal type, is rarely primary, but 
originates as an extension process from the middle ear or the pharynx. 
The tube is closed by swelling of its wall and the collection of exudate, 
thus preventing the passage of air from the pharynx, so that decreased 
pressure exists in the tympanum from absorption of the air therein. 
Continued or recurrent inflammations lead to stenosis of the tube, 
damage to the ear, and deafness. 

Obstruction of the Eustachian tube also results from hypertrophic 
mucous membrane about its opening in the pharynx, or by negative 
pressure when the nasopharynx is obstructed by adenoids. This 
decreased pressure draws the mucosa of the tube downward and col- 
lapses the lumen at the same time. 

THE INTERNAL EAR 

Circulatory disturbances of this part of the ear are similar to 
those given for the tympanum. Hemorrhage is, however, more serious, 
as it almost always leads to nerve-fiber degeneration, even though 
quickly absorbed. 

In acute infections, leukemia, and pernicious anemia the. hemor- 
rhages are small, while in trauma they may be rapidly spreading and 
destructive. Hemorrhagic extravasation occurs in Meniere's disease, 
partly, however, of inflammatory origin. 

Inflammations in the internal ear are secondary to disease in the 
middle ear or cranium by extension, or to conditions elsewhere, the blood 
then bringing the bacteria. The processes are usually acute and follow 
the pathological changes given for the tympanum, except that to these 
features must be added alteration of the special sense organs, which 
easily undergo degeneration and are probably never replaced. Caries 
and necrosis of the bone frequently occur. When the process is more 
fibrous one thinks of its probable syphilitic origin. The suppuration 
in the internal ear spreads to the tympanum or to the skull, to the 
latter traversing the internal auditory canal along the sheath of the 
,auditory nerve. This is also the course followed in reverse, when menin- 
gitic inflammation invades the middle ear. 



CHAPTER XVII 



THE SKIN 
ANATOMY 

The skin consists of two layers: the epidermis, composed of stratified 
epithelium; and the cutis, a layer divided into corium, or true skin, and 
the supporting connective tissue below. Some epithelial structures, 
hair-follicles, sebaceous and sweat-glands, lie in the cutis and subcu- 
taneous tissues. The epidermis consists from without inward of a horny 
layer of flat translucent cells beneath which is a clear layer of shining 
cells containing an albuminous substance, eleidin. The next deeper 
layer is composed of the granular cells of the rete Malpighii, in which 
lie granules of keratohyalin. Below this are the polygonal cells of 
the prickle-cell layer lying upon the deepest, or basal cells; these last 
are ovoid or short cylindrical epithelia. In all the layers of the rete 
protoplasmic bridges pass from one cell to another. The basal epithe- 
lium is the youngest and grows outward to form the upper rows. It 
rests upon a hyalin basement-membrane, separating the epidermis 
from the corium. The corium is divided into the papillary and reticular 
layers. The epithelium follows the curves made by the papillae of the 
upper layer. The stalk of the papillae is made up of delicate elastic and 
collagen fibers and blood-vessels, while deeper down the connective 
tissue runs in stout bundles. The subcutis is a looser adipose and 
connective-tissue layer of quite irregular thickness. 

Hair-follicles lie in the corium or subcutis surrounded by a thick 
fibrous mantle, within which is a hyalin basement-membrane carrying 
cuboidal epithelium. In the epidermis and to the openings of the 
sebaceous glands, all layers of epithelium follow the line of the hair- 
follicle. Sebaceous glands open upon the hair-follicle in the malpighian 
layer. These glands are racemose in form and the cells correspond to 
the deep epidermal cells. At the base of the hair-follicle is a papilla of 
connective tissue upon which rests the group of epithelial cells which 
form the matrix of the hair. 

The sweat-glands are long tubular structures with a coiled internal 
extremity and a spiral passage through the epidermis. 

The blood- and lymph-vessels of the true skin are very numerous 
and anastomose freely. The nails are stratified layers of horny epi- 
thelium arising in a bed made of large papillae and a wide basal epi- 
thelial layer. The pigment of the skin lies in the deep layers of the 
rete of the epidermis and in the corium. It is iron-free melanin, and 
made by chromatophores in the corium. 

It is impossible, within the space allotted to the subject in this book, 
to give more than the general characters of diseases of the skin. The 
subject has been greatly studied, but microscopical examination reveals 

990 



THE SKIN 



991 



much less than the clinical observation would warrant one to expect. 
The skin is in close relationship with some of the internal organs, and is 
so extensive and in such an exposed position that its lesions are numer- 
ous and varied. They are here considered from the standpoint of 
general pathology, with little reference to the clinical manifestations. 

CONGENITAL ABNORMALITIES 

Nevus is the most important congenital defect, although not the 
only one, since whole sections of skin surface may be missing. Nevi 
appear in the following forms : 

Simple angiomatous telangiectasis, wine stain, a flat or slightly 
raised red or purple stationary growth. 

Cavernous angioma, a cystic angioma of blue color. 

Pigmented nevi consist of angiomatous, fibrous, and epithelial hy- 
perplasia, carrying pigment both in epithelial and cuticular layers. 
They may be flat or raised, minute or very extensive, smooth, hairy, 
or uneven. Microscopically, one finds masses of epithelioid or endothe- 
lial cells in the corium about which pigment is deposited. 

Sebaceous nevi are flat or slightly raised yellow areas, commonly 
on hairy parts, the result of increase in the sebaceous glands. 

Atypical epithelial growths of surface or glandular cells, congenital 
in origin, sometimes form raised cystic or solid benign epithelioma 
adenoides. Lymphangiomata of congenital origin sometimes occur in 
the skin. 

ATROPHY, HYPERTROPHY, AND DEGENERATIONS 

Atrophy of the skin occurs in senility, as the result of lowered nutri- 
tion as in neuritis, after prolonged undue stretching, and, secondarily, 
in constitutional diseases like diabetes or tuberculosis. The epithelial 
layer becomes thin, the lower cells are irregularly pigmented, the 
papillae are flattened, the hair-follicles shortened, the hairs become 
wooly or cease to form, the sebaceous glands distend and empty their 
secretion into the hair-follicles so that both cavities distend to a cyst 
or teen. The collagen or even the elastic fibers of the corium undergo 
hyalin or granular degeneration. Sweat-glands are usually well pre- 
served. 

Hypertrophy of the skin may affect either layer or both, but in 
any case one layer has more prominent changes than the other. In 
hypertrophy of the epidermis there is a condition termed hyperkera- 
tosis in which there is reduced desquamation of the horny layer, the 
cells adhering closely to one another, and the whole layer is firmly ap- 
plied to the rete, the cells of which may show active proliferation. 
The commonest epidermal hypertrophy is the callosity, due to pressure 
or rubbing, in which the granular layer of epithelium increases and 
assumes a dense homogeneous yellow appearance. On the other hand, 
the rete cells may be pressed down, distort the papillae and upon them 
collect into softened masses, or corns. Cutaneous horns, not infre- 
quently of congenital origin, are due to hyperkeratosis with down- 



992 



A TEXT-BOOK OF PATHOLOGY 



growth of the basal epithelium into the corium, the papillary layer of 
which is distorted and may show branching. 

Ichthyosis is a congenital or acquired condition characterized by 
the occurrence of large plates of horny epithelial crust or scales. Under 
the microscope one finds great widening of the horny layer with plugs of 
homogeneous epithelial cells filling the outer part of the hair-follicles. 
There is often excess of pigment in the epithelium lying upon the 
corium, but the granular epithelial layers may be missing. Not infre- 
quently a mild fibrous thickening of the corium exists, which in con- 
genital or long-standing cases leads to atrophy. In congenital ichthyosis 
the body is covered with dry folded or scaly skin, traversed by deep 
fissures, giving the appearance of crocodile skin. In the acquired form 
the skin is dry, shining, pigmented, and covered with friable crusts or 
scales separated by cracks. 

Warts, or verrucas, are composed of hyperplasias of horny and 
prickle cells with a slight increase in the corium, while in condylomata 
there are thickenings of both layers. Perhaps the most pronounced 
part in these formations is taken by the papillary layer, which may 
grow out like long villi, the surface being covered with very much thick- 
ened epithelium. The process is both a hyperplasia and hypertrophy. 
The connective tissue in both these growths is very rich in blood-vessels. 
Some leukocytic infiltration appears. Both these hypertrophies are 
said to be contagious, and this seems surely true of the condylomata, 
as they are frequently associated with venereal disease and appear most 
often around the genitals. 

The pathology of those conditions affecting the outer layer, or both, 
having been discussed, it remains to consider the hypertrophies most 
prominent in the corium. The principal features are increase in the 
elements natural to the membrane, but to this is added fibrotic changes 
which naturally follow increase of blood, or succeed upon continued 
irritation. 

Scleroderma is a diffuse or disseminated hypertrophy of the skin 
of unknown cause, but thought to be associated with nervous or thyroid 
disease. The skin is hard, firm, and stretched. Under the microscope 
one finds increase of connective tissue arranged in bands. The skin, 
muscles, and subcutaneous tissues are involved. The blood-vessels 
show chronic thickening of all their walls, including obliterating end- 
arteritis. Atrophy soon arrives and leaves a dry, lifeless surface. The 
epidermis does not suffer. In the congenital forms, called sclererna, these 
lesions are associated with edema, while in the fatty form the corium 
has a yellow fatty appearance which may or may not be due to true fat. 

Elephantiasis is a chronic thickening of the corium and deeper 
tissues of unknown origin in some cases, while others are due to fila- 
ria in the lymph-vessels (tropical form), to passive congestion, chronic 
dermatitides, like eczema, and to mechanical lymph and blood stasis. 
The skin is greatly increased in its whole depth, stiff, and cannot be 
folded, which pachydermatous condition gives the disease its name. 
Marked disfiguration of legs or other parts is common. The disease 



THE SKIN 



993 



is especially common in the scrotum. Connective tissue increase from 
the epiderm to the muscles is found by histological study. Elastic 
fibers are decreased in number. The vessels are fibrosed and throm- 
botic. Glandular structures soon atrophy. 

Necrosis of the skin may be due to injury, or disease of nerves or the 
spinal cord, and is exemplified in pressure sores (decubitus). There is 
at first redness and swelling, followed shortly by dense infiltration 
and dry hardness of the part. Shortly, blisters or blebs form, and the 
deeper tissues degenerate. An ulcer soon appears with swollen red- 
dened edges, a slough is cast off, and healing occurs by scar formation. 
The latter part of the process may be considered as gangrene. Gangrene 
of the severer grades, aside from the cases arising from nervous diseases, 
may follow injury, especially where blood-supply is cut off and cannot 
be established by collateral means, freezing and burning. In diabetes 
and ergotism the cause is not clear. In these cases multiple areas of 
gangrene are common. Senile gangrene of the foot begins in the skin. 
Some gangrenes, like noma, result from the introduction of masses of 
bacteria, mostly anaerobic, through wounds. 

Symmetrical gangrene of Raynaud is multiple and appears upon 
corresponding parts of both sides of the body (fingers, ears). It is 
probably due to combined nerve and vascular defect. Perforating 
ulcer of the foot is a form of local gangrene depending upon neuro- 
trophic disturbances. 

Regeneration of the superficial skin takes place perfectly when the 
defect has not been deeper than the papillary layer. The rete, from the 
edges of the defect, grows together until it covers the surface. If, 
however, the corium has been damaged, scar tissue results, and the 
defect is replaced by a fibrous tissue poor in vessels and cells. The elastic 
tissue may be imperfectly replaced, but the glandular structures are 
missing. If the fibrous tissue be excessive, a prominent hypertrophic 
scar remains. Atrophic skin is replaced by scar tissue, but traces of 
the essential tegumentary structures remain. 

VARIATIONS IN PIGMENTATIONS 

Increase of the pigment affecting a large part of the body occurs in 
Addison's disease and upon exposed parts after exposure to the sun. 
Local increase of pigment is found in freckles, in chloasma, or "liver 
spots." Presence of abnormal pigmentation is seen in jaundice and 
certain poisonings like that from silver. Increase of pigment may be 
seen after the absorption of hemorrhagic extravasations. 

Decrease of the general pigment is exemplified by albinism. Local . 
decrease is seen in vitiligo and in scars. 

CIRCULATORY DISTURBANCES 

Anemia may be general or local. The former is seen in anemia, 
hemorrhage, and shock. Local anemias are due to cold, vasomotor 
neuroses like Raynaud's disease, or obstruction to the circulation. 

63 



994 A TEXT-BOOK OF PATHOLOGY 

Hyperemia. — Active hyperemia is the result of irritation, excessive 
warmth or cold, or of internal vasomotor conditions due to toxic or 
infectious causes. Small local hyperemias are called roseola; general 
reddening is erythema. 

Passive hyperemia, cyanosis, or blue skin, may be general in cases 
of venous obstruction near the heart, and in circulatory disease due 
to heart and lung disorders. It is then most marked in the extremities 
and face. Prolonged pressure hyperemia may lead to edema, or to des- 
quamative, sclerosing, or atrophic dermatitis. 

Hemorrhage into the skin takes the form of petechise, ecchymoses, 
vibices (linear), and hematoma. It may occur in the corium alone 
or find its way to the epidermis. Its characteristic is that it produces a 
dark red or purple stain that cannot be pressed away. Hemorrhage is 




Fig. 459. — Urticaria — section of a wheal: e, Epidermis, practically no alteration; c, 
corium, showing acute inflammatory changes, swollen and infiltrated with serous exuda- 
tion, with the blood-vessels (v, v, v), especially those accompanying the sweat-ducts 
(s, s, s, s), dilated and surrounded by and containing numerous polynuclear leukocytes; 
lymphatic vessels (I, 1) and spaces also enlarged, containing granular matter; numerous 
mast-cells (m, m) scattered through the corium (courtesy of Dr. T. C. Gilchrist). 

met with after some injuries, in infectious diseases, and in the various 
purpuras. 

Edema of the skin is the doughy condition arising when the venous 
circulation is cut off, the lymph flow obstructed, or the vessel walls 
and tissue tension changed, as . in nephritis. It occurs also in what is 
called neuropathic, angioneurotic, or toxic edema (Quincke's edema, after 
eating shell-fish, fruit, etc.), the cause of which is not known. Urticaria 
is a local edema due to irritation or as a part of the last-mentioned 
group, and takes the form of circumscribed cellular edema of the co- 
rium, showing upon the surface as firm, flat, pale elevations with a 
pink margin (hives, dermatographia). 

INFLAMMATION (DERMATITIS) 

The inflammations of the skin are exudative in character for the 
most part, but are accompanied by certain hyperplastic, degenerative, 



THE SKIN 



995 



and desquamative processes in the epidermis which lend to them at 
times a catarrhal appearance. Changes in one layer without concom- 
itant alterations in the other are rare. Following the plan noted in an 
earlier paragraph, there will be given here the pathological manifesta- 
tions in the various layers without dwelling long upon the clinical 
appearances, the most important objective factor in the study of dis- 
eases of the skin at the present day. 

The causes of dermatitis are numerous and varied. They embrace 
injuries of various kinds by heat or cold; chemical and mechanical 
agents; intoxications by exogenous or endogenous substances; infective 
vegetable and animal organisms, and they may be the result of altered 
nutrition from faulty innervation or blood-supply. The cause of many 
dermatitides has not been discovered. 

The evidences of inflammation of the skin fall into certain fairly 
well-defined classes, and it is perhaps well that the reader be familiar 
with the terms given to the eruptions and their pathological meaning. 

Erythema is diffuse reddening of the skin with or without swelling, 
and subject to great variations. 

Macules are non-elevated, clearly outlined areas, presenting any 
color known to the skin. The size is usually small. 

Papules are elevated areas of various shapes, usually small and 
with clear margins. . A mixture of these last two is known as a maculo- 
papule. 

Tubercles are sharply outlined firm swellings larger than papules, 
and sometimes warty in appearance. 

Vesicles are localized collections of clear fluid the size of macules or 
papules, within the epidermis or between it and the corium. 

Bullae, or blebs, are large vesicles arising by separation of large 
areas of epidermis from its base by fluid, or by coalescing of vesicles. 

Pustules are vesicles containing pus. If very large, they are called 
ecthyma. 

Crusts are masses of dried exudate and epithelium. 
Scales are sheets of dead epithelium. 

The simplest inflammations of the skin, such as are found in scar- 
latina, in food-poisoning, or in idiopathic erythema, take the form of 
congestions of the corium, with varying grades of transudate or even 
cellular exudation. This may be confined to the corium and epidermis, 
but in the more severe grades, as scarlatina, it penetrates to the sub- 
cutis. These conditions are for the most part devoid of exudate upon 
the skin surface, but are followed at times by scale formation. The 
inflammation may be diffuse, as in measles or food-poisoning, or local- 
ized, as in erythema nodosum. 

The next higher grade of inflammation is indicated by more intense 
edematous and cellular infiltration of the upper layers of the corium, 
with penetration of the fluid to the malpighian epidermal layer. The 
fluid pushes aside the cells of the basal and prickle cell layers, where it 
may form vesicles, being held in place by the horny layer through which 
the fluid cannot pass. The deep epithelium becomes necrotic and softens, 



996 



A TEXT-BOOK OF PATHOLOGY 



a process which may be due to the actual cause of the dermatitis in 
some cases, and is, therefore, primary. The vesicles may dry and cover 
themselves with a crust, or break and leave a weeping surface. The his- 
tological changes in the corium are cellular edematous swelling of the 
papillary layer, congestion, and perivascular collections of round cells. 
For examples of this process one can turn at first to herpes in any of its 
various forms. This condition presents patches of small vesicles tightly 
filled with clear or slightly cloudy fluid, surrounded by an areola of 
swollen injected skin. The vesicles are situated in the deep layers of the 
rete. The cause of herpes is not known, but the disease is thought to be 




Fig. 460. — Pemphigus — a beginning bleb (a) between corium and the epidermis, the 
bared papillae (6) forming the base; acute inflammatory changes in the papillary layer of 
the corium, with marked serous exudation, particularly about the vessels; reticular part 
of the corium and the sweat-glands (s, s 3 , s 4 , s 5 ) are practically normal, except where the 
sweat-ducts (s lt s 2 ) are involved in the bleb-formation: d, corneous layer; e, rete; v, v, 
blood-vessels; c, cell masses at base; /, about the natural size of bleb examined (courtesy 
of Dr. T. Caspar Gilchrist). 

due to nerve irritation or an infectious agent. A more extensive 
vesicular process is found in pemphigus. Here one finds large bullae 
upon normal or slightly swollen bases, with clear or slightly cloudy con- 
tents. The cysts arise by exudation between the corium and 'the epider- 
mis, although at times some epithelium is seen lying upon the papillae. 
The blebs become purulent, burst, or dry and form crusts. The cause 
of the various forms of pemphigus is not known, but it frequently 
appears upon syphilitic newborn children. 

Frankly infectious forms of vesicular dermatitis are varicella, -variola, 
and impetigo. The first and the last form their vesicles fairly high in 
the epithelial layer, while the variola virus causes an early degenera- 
tion of the basal cells of the rete malpighii, to which suppuration is 



THE SKIN 



997 



soon added. Impetigo is a disease due to some pyogenic organism; 
the vesicles are always purulent, and leave crusts upon a granulating 
surface. 

Severe insults to the skin, like burning, freezing, and concentration of 
light rays, produce an exudative dermatitis with fluid collections in the 
epidermis. This result is due both to exudation and damage to the 
epithelium itself. The vesicles, or blebs, are filled with serum, which 
may escape by rupture of the horny layer, thus , leaving a weeping 
surface. In the severer burns this stage is short, a slough forming very 
early. In freezing, the same lesions may appear, but gangrene is more 
apt to occur. 

Eczema.— This affection of the skin with its protean manifestations 
belongs in the exudative class because, with the exceptions of the very 
destructive or very old cases, the lesions, under the microscope, are 




t 



Fig. 461. — Eczema seborrhoicum, section of a small papule in the type commonly 
known as "seborrhcea corporis." A hyperplastic horny layer and dense inflammatory 
cell-infiltration in more or less of the entire corium, with slight edema (courtesy of Dr. 
Geo. T. Elliot). 

essentially the same as in the immediately preceding groups. Clinically, 
the disease has innumerable modifications, but it commonly begins as 
an erythematous or vesicular dermatitis. The infiltration and swelling 
of the papillary layer are marked, especially about the enlarged blood- 
vessels and lymph-channels. Vesicles occur in the usual manner by 
destruction of the deeper epithelium by pressure, but in their absence an 
excess of fluid is present in the epidermis. This fluid finally finds its way 
to the surface and the superficial cells are removed in crusts. To replace 
the lost surface cells the deeper layers actively push out and new super- 



998 



A TEXT-BOOK OF PATHOLOGY 



ficial layers are formed without the normal keratin (parakeratosis). 
This leaves a surface covered with cells of the malpighian layer, a softer; 
pinker, more sensitive, and probably weeping area. In chronic cases, 
however, especially of the dry varieties, there is a hyperkeratosis, a 
condition in which the excessively produced epithelial cells are not 
desquamated, but remain as crusts or scales. The papillae are variously 
altered also by fibrosis in chronic cases. The cause of eczema is un- 
known. It has been ascribed to infection and endogenous or exogenous 
intoxication. 

The consideration given to the imperfect formation of the horny 
epithelium in eczema leads to a discussion of those inflammations in 




Fig. 462. — Eczema — sluggish, deep-seated, vesicular type, with scattered lesions and 
somewhat thickened corneous layer, commonly seen on the fingers; section from palmar 
surface of a finger (low magnification) : a, a, Represents a vesicle in the earliest observable 
stage; the mucous layer in the lighter part shows molecular changes, and corresponds to 
the area of inflammation in the papillary layer of the corium below. The papillae show 
marked serous exudation, dilated blood-vessels, and invasion of leukocytes (courtesy of 
Dr. A. R. Robinson). 

which, by reason of faulty nourishment of the epithelium from the 
corium or functional disarrangement of the deeper layer of the epidermis, 
an abnormal or excessive production of horny epithelium (para- or 
hyperkeratosis) takes place and expresses itself in cast-off scales of various 
dimensions. In those conditions where the frank inflammatory lesions 
recede, less fluid passes through the rete malpighii, but, nevertheless, 
a disturbance of this layer exists. It consists in a separation of the 
cells, degeneration of some of them, and irregular hyperplasia to make 
up for the cast-off superficial layers. Irregular horny layers are produced 
and cast off because of the lesions below, which consist of fibrous changes 
of the papillary layer, or even deeper. In this class fall psoriasis and 



THE SKIN 



999 



lupus erythematosus. In psoriasis the horny layer is increased in 
thickness, and the cells separated by leukocytes, organisms, and air, 
to the last of which the silvery sheen of the crusts is ascribed. The 
rete cells are separated and hyperplastic and fluid lies between them. 
Keratohyalin is lacking. Distinct thickening occurs in the corium and 
the papilla? are irregular. 

To this exfoliative class belongs also pityriasis rubra, a condition in 
which the corium changes are equal in importance to the epithelial, and 
which goes on to atrophy. 

In lupus erythematosus the corium shows fibrous thickening and 
obliterating endarteritis which lead to atrophy and cicatrization. The 
epithelial layer is thickened, broad scales lying upon the hyperplastic rete. 

Papular eruptions are known in many skin diseases. As would be 
expected, the chief seat of the swelling is in the corium, where a local- 




Fig. 463. — Psoriasis — from a chronic patch — showing marked hyperplasia of the rete 
extending deeply downward as interpapillary prolongations, thus giving the papillae in- 
creased length. The secondary inflammatory changes in the corium are seen, with enlarge- 
ment of the blood-vessels (a), in the cutis proper as well as the papilla;, and extensive 
(b, b) perivascular cell-infiltration (courtesy of Dr. A. R. Robinson). 

ized cell and fluid infiltrate occurs. To this may be added a hyperplasia 
of the epithelial layer, the cells of which are separated by fluid or leuko- 
cytes. True vesicle formation may occur on top of a papule. In other 
cases the papule may be caused by an increase in the rete epithelium 
alone, either on the free surface or at the openings of glands. Prurigo 
and lichen belong to this class of pathological changes in pure form, 
but it should be remembered that papules may occur in almost any 
dermatitis. 



1000 



A TEXT-BOOK OF PATHOLOGY 



Inflammation Chiefly Affecting Hair-follicles and Sebaceous Glands. — 
These two structures are usually involved together by reason of their 
close anatomical association. An obstruction to the outlet of the 
follicle dams back secretion, and bacteria, sinking in along the hair, 
easily invade the gland. Obstruction can take place when accu- 
mulations of epithelial cells and sebaceous material become dried 
about the hair. This may hold back the secretion until it becomes 
hardened into a comedone. If this retained secretion becomes infected 




Fig. 464. — Lichen planus — section from a chronic patch (moderately high magnifica- 
tion) : a, b, c, Show respectively the corneous layer, granular layer, and rete — all consider- 
ably thickened; e, e, microscopical cavities, with serous exudate; d, corium, infiltrated with 
exuded round cells, and with marked increase in the size of the connective-tissue corpuscles 
(courtesy of Dr. A. R. Robinson). 

by pus cocci, various lesions arise. In some, as sycosis, the hair-follicle 
and its surroundings show the most effect, while in acne of the simpler 
variety the disease is fairly well limited to the sebaceous gland. 

Acne vulgaris is an adenitis or folliculitis, expressed by small pus- 
tules and a mild concomitant dermatitis, due to bacterial infection. 
Some persons seem to have a special disposition to it, especially at 
puberty. It may occur after the use of bromids and iodids. Sycosis 
is probably due to a mould. It is a folliculitis chiefly near the skin 
surface, but may extend deeply into the sebaceous gland. 



THE SKIN 



1001 



Acne rosacea is a diffuse sclerosing dermatitis with increased seba- 
ceous secretion from hypertrophic glands which may or may not show 
inflammatory changes. It occurs commonly on the nose and cheeks 
as a red, irregular, uneven, or nodular patch. Vessels are large and dis- 
tended; fibrous tissue is increased and may constrict the sebaceous 
gland ducts. 

Furuncle is a localized suppuration of the skin starting in a sebaceous 
gland, and characterized by the formation of a central necrotic slough 
and a densely infiltrated wall separating it from the healthy tissue. 
This wall is not sharply defined, but fades into healthy parts. The 
cavity, after evacuation, heals by granulation. Furuncles are due to 
the pus cocci penetrating the follicles, especially when favored by slight 
injury. 

Carbuncle is a compound furuncle formation characterized by soft 
necrotizing spread and multiple sloughing openings in the skin. This 




is due to staphylococci or streptococci. General lowered vitality 
favors the inflammation, and furuncles appear as skin complications 
in diabetes, marasmus, and the like. 

Malignant pustule, or anthrax, is a localized suppurative and gan- 
grenous process. There occurs rather superficially a dark red or brown 
edematous and indurated swelling which soon softens in the center, 
but underneath there is a firm slough. The minute pictures show a 
purulent collection containing anthrax bacilli in the deeper epithelial 
layers, elevating the epidermis from the papilla?. The inflammatory 
process in these last three conditions is one of fibrinous, purulent, and 
liquefactive character. 

Inflammations Chiefly Affecting the Corium and Subcutis. — Diffuse 



1002 



A TEXT-BOOK OF PATHOLOGY 



inflammations take the form of infiltrations, which range from simple 
edema with congestion to suppuration. They all tend to spread, 
but in so doing are preceded by a zone of congestion or dense infil- 
tration. The simplest of these processes is erysipelas, an acute 
or subacute infection due to streptococci. There is congestion and 
serous or serofibrinous infiltration. Cellulitis is next in severity, 
affecting chiefly the subcutaneous tissue, although the true skin is almost 
alwavs infiltrated. In this lesion there is extensive fibrinous and cellu- 




lar exudate. It is commonly the result of infection through the lymph- 
atics. Phlegmon is the name given to a true suppuration in the corium 
and subcutis. It is a rapidly spreading purulent infiltration, which may 
break outward and discharge, or penetrate the muscles inward. 

Ulcers of the skin, be they infectious, like soft chancre, or due to 
metastasis through lymph- or blood-stream, begin by serous or serocellular 
infiltrate of the deeper epidermis with extension outward and inward. 
Of course, whole sections may be discharged when phlegmon has isolated 
an island of skin by cutting off its nutrition. 



SPECIFIC INFLAMMATIONS 

Under this heading come the class of infectious granulomata and 
mycotic diseases. The etiology and histopathology of the former have 
already been discussed (see Chapter V), and it remains to be pointed out 
here how they appear in the skin. 

Tuberculosis of the skin, or lupus, may be primary or secondary, 
in the former case being directly inoculated into wounds. It occurs in 



THE SKIN 



1003 



many forms, as flat thickenings, as uneven, slightly raised areas, 
or as excrescences, or even verrucse. The tuberculous process as- 
sumes the diffuse fibrous form, with here and there giant cells, and 
an occasional fully formed miliary tubercle. There is little tendency 
to caseation in the ordinary sense. The seat of the lesion is the 
corium, the supporting fibers of which layer degenerate. There are 
numerous lymphocytes and mast cells about the infiltrate. The epi- 
dermis is little affected, except in the warty inoculation form, when 
it may be thickened in the horny layer. Tubercle bacilli are difficult 
to discover in the lesions of lupus. General fibrosis of the lesion is a 
common method of healing, and scar tissue is extensive and disfigur- 
ing. The common form is known as lupus vulgaris, which appears 
usually upon the face. The primary inoculation, or warty form, is 
lupus verrucosa, seen oftenest upon pathologists, veterinarians, and 
butchers. Two forms of ulcerative tuberculosis of the skin in early 
life are the miliary and scrofuloderma, the latter being common near 
caseous glands, and seeming to be an infiltration with fibrosis and 
atrophy due to the adjacent lesion. 

Syphilis. — The primary lesion, or chancre, occurs usually on the 
genitals, but may be implanted anywhere. It appears as a hard mass, 
occupying all layers of the skin, and shows a tendency to early ulcera- 
tion. The firmness is due to a dense infiltration and proliferation in the 
whole corium, being diffuse in the papilla?, and close about the blood- 
and lymph-vessels lower down. Multiplication of connective-tissue 
cells soon appears. The Spirochsetas are found everywhere, but espe- 
cially near the vessels and in their walls. 

The secondary lesions may assume any form of eruption known to 
the skin. They have a tendency to be pigmented and polymorphous. 
Early in the disease the eruption is symmetrical, but later it is com- 
monly localized. Histologically, there is an infiltrate of small round 
cells in the papillary layer and increase of connective-tissue cells here 
and there deeper in the corium. Exudates of fluid character may appear 
either in the papillary layer or rete malpighii. 

Gumma, or the tertiary lesion, appears as a firm swelling, rather 
deep in the skin, which shows a tendency to soften and ulcerate outward. 
(See Histology of Gumma.) Spirochceta pallida are numerous in the 
secondary lesions, especially those giving a moist surface (condyloma 
latum), but they are found with difficulty in gummata. 

Leprosy. — The lesions of leprosy take place in the corium and 
subcutaneous tissue, and seem to have a predilection for nerves and their 
surroundings. They compress glandular structures. Connective tissue 
overgrowth is common in later stages. 

Actinomycosis and glanders occur in the skin by direct inocula- 
tion or by extension. The process is one of necrotizing cellulitis sur- 
rounded by granulation. 

Mycosis fungoides has been described (see page 199). 

Mycoses of the skin are caused by moulds (hyphomycetes), which 
invade the epidermis and the structures arising therefrom, especially 



1004 



A TEXT-BOOK OF PATHOLOGY 



the hair-follicles. Blastomyeetes also produce a dermatitis, but pene- 
trate to the corium or are brought thither by the blood or lymph. 

Favus is an inflammatory mould disease presenting yellow concave 
crusts, or scutula, which are made up of the mycelium of the moulds 
and epithelium. These are well fastened to the deep horny layer. 
The mould may penetrate the hair-follicle, and in the epidermis is 
found a leukocytic infiltration. The mould is Achorion schdnlemii. 

Tinea, or ringworm, is a dermatomycosis due to members of the 
genus Trichophyton. 

Tinea tonsurans gives a dirty gray crust of mould and epithelium 
upon hairy parts. The hairs are broken by the growth of mould within 
and around the hair. The base of the eruption is round and consists 
of swollen, slightly indurated skin, which may or may not be inflamed. 

Tinea circinata is probably a result of the same infection as the last, 
but occurs in less hairy parts of the skin. It grows in a spreading circu- 
lar manner by the spread of moulds within the deep epidermal layers. 
A mild congestion of the corium occurs. 

Tinea sycosis, also of trichophyton nature, occurs over shaven 
beards, and is due to the growth of mould into the hair-follicle and 
sebaceous gland. It is aeneiform in appearance. 

Tinea, or pityriasis versicolor, is a desquamative condition due to 
the presence of Microsporon furfur in the horny epithelium. There 
are yellowish, reddish, or brownish spots covered by scales. There is 
little inflammation. 

Erythrasma is a scaly eruption upon warm and moist parts. It 
is said to be due to a microsporon species. 

Blastomycosis and the related coccidioidal granuloma (see page 
348) are specific inflammations of both the epidermal and dermal layers. 
The affections present a diffuse thickening of the skin, with warty and 
ulcerative eruptions similar to epithelioma and tuberculosis. Papules 
or pustules may form. The lesions in the epiderm are infiltration of 
polynuclears between the deep epithelial layers, the cells of which are 
swollen and separated, and hyperplasia with irregular prolongations 
into the corium. Abscesses form, in which may be found the round 
or elliptical yeasts. Prickle cells are prominent, a feature which, when 
combined with the miliary abscesses, is very characteristic. The horny 
layer is widened and irregular. In the corium are small abscesses con- 
taining the organisms, a diffuse granulation tissue with cells of the 
small lymphoid series, endothelium, and, occasionally, a giant cell. 

Dermatitis Due to Animal Organisms. — The most important form 
is scabies, the itch, due to the Acarus scabiei, an arthropod. The 
female burrows a track in the horny epithelium, where she lays her 
eggs. These hatch out, and the young burrow further. The inflam- 
mation that follows is due more to scratching than to the parasites, 
which, however, have some irritative action. Pediculi (lice) and fleas 
bite the skin, and produce an irritation. The dermatitis that appears 
is due to scratching, and may in prolonged cases take the form of a 
weeping eczema. 



THE SKIN 1005 

Epithelioma or molluscum contagiosum is a flat or slightly raised, 
firm mass supplied with a central depression and opening, having a 
waxy or pearl-like color, commonly the size of a pea, and situated most 
often upon genitals and head. By some its contagious character is 
denied. It consists, under the microscope, of radially arranged hyper- 
plasia of the rete malpighii, separated into lobes by fibrous projections 
of the corium, which layer is much distorted by this downgrowth. 
In the center is a mass of desquamated cells and detritus which can be 
pressed out of the gross lesions. The rete cells are degenerated and 




Fig. 467. — Molluscum contagiosum: a, Lobular epidermal growth; 6, molluscum bodies; 
c, detritus as contents of central spaces (Aschoff). 

many contain the so-called "molluscum bodies." These are clear spaces 
situated near the nucleus, and may at times or by special stains show 
an amorphous chromatic mass. They are probably degenerative or 
may be included with the Chlamydozoa. 

TUMORS 

Fibroma is the commonest benign tumor of the skin. It appears as 
single large, firm swellings, or as multiple soft growths, sometimes indi- 
vidually, at others in groups, which arise from the connective tissue of 
nerve-sheaths (neurofibroma). Keloid is another fibromatous tumor of 
the skin. 

Lipoma occurs as single large, lax masses, or as multiple small 
growths, which may be symmetrically distributed. Xanthoma is a 
tumor related to lipoma, appearing as yellow plates or warty masses. 



1006 



A TEXT-BOOK OF PATHOLOGY 



It lies in the corium, and consists of connective tissue surrounding 
groups of fat-like, refractile bodies (xanthoma bodies) and clusters of 
epithelioid and multinucleated cells, arranged usually near blood-vessels. 
This tumor occurs in diabetes and occasionally in icterus. 

Myoma sometimes occurs in the skin, as do osteoma and chondroma. 

Angioma has been considered under Nevi, but those tumors consist- 
ing of vessels and proliferated lining membranes, the endo- and peri- 
theliomata, are occasionally met in the skin. They are related to — 

Sarcoma. — This tumor in its pure form is rather rare in the skin, in 
which it has been known to take any form. By far most frequently 
the melanotic form is seen. These tumors arise from nevi and develop 
in spindle cell or alveolar form. They contain atypical chromato- 
phores. A special form is the idiopathic multiple pigmented sarcoma 
of Kaposi, a disseminated variety of granulomatous and angiomatous 
nature. 

Epithelial tumors are the commonest new growths of the skin, 
and appear as epitheliomata and glandular cancers. 

The squamous epithelioma appears as a nodular growth, tending to 
ulcerate early, to spread out, and to be surrounded by a hard raised 
edge. It grows downward into the deeper tissues with finger-like pro- 
jections visible to the naked eye. Under the microscope there are 
numerous pearls in the closely packed epithelial masses. The com- 
monest seats for this growth are where skin and mucous membranes 
join. Metastasis to the lymph-glands is common. ■ 

Rodent ulcer is an epithelioma in which the actively growing tumor 
cells retain more of the shape and size of the basal cells of the rete 
malpighii than is the case with the preceding form. The cell masses 
are in the form of anastomosing columns, and have few or no pearls. 
Paget's disease of the nipple is of this character. 

Carcinoma basocelhdare of Krompecher retains throughout the basal 
cell characters and grows as rounded nests containing central degenera- 
tive cysts, or as branching tubular cell projections. 

Benign cystic epithelioma is one of the new growths retaining the 
basal cell characters, said by some to grow from sebaceous cyst ducts, 
by others from hair-follicles, and by still others from the rete of the 
surface epidermis. 

Lenticular carcinoma, or cancer en cuirasse, is that form which 
tends to spread under the skin, causing dense infiltration. It is usually 
secondary to cancer of the mamma. Carcinoma of the skin arises 
from its glands, and is discussed later. Secondary malignant tumors 
are not common in the skin. 

Structures Within the Skin 
sebaceous glands 

Seborrhea is a hypersecretion of sebaceous matter which may give 
rise to a scaly seborrhea siccum when a mixture of sebum and epi- 
dermal scales dry upon the surface, or seborrhea oleosa if the skin remains 



THE SKIN 



1007 



oily; dandruff and smegma in excess are respective examples. If pro- 
tracted in duration and excessive in degree, a complete dermatitis may 
arise. 

A osteatosis is a deficiency of sebum, and is a constant companion 
of many dermatitides, but is rare as a primary process. 

Comedo is the accumulation of inspissated sebum held within the 
gland by a plug of epithelium, dried sebum, and dirt in the opening 
of the hair-follicle. The cause is probably a hyperplasia of the super- 




ficial gland cells, although it may have a deeper significance, since it is 
so constant at puberty as to be almost physiological at that time of 
great activity of the skin. If the hyperplasia be prolonged, acne results. 

Wens, or sebaceous cysts, may be considered as an exaggeration 
of the foregoing, the enlarged gland being surrounded by a connective- 
tissue capsule. 

Milium is the appearance of small pale masses, the result of accumu- 
lation of sebum in the gland when the duct is completely occluded. 
Acne. — (See page 1000.) 

Tumors. — Adenomata, simple or of the cystic papillary type, and 
true carcinomata are known. 

SWEAT-GLANDS 

Hyperidrosis and anidrosis are respectively excessive and deficient 
or lacking sweat secretion. They may be associated with other dis- 
orders, but are obscure in origin otherwise. 



1008 



A TEXT-BOOK OF PATHOLOGY 



Bromidrosis, or malodorous sweat, is usually a peculiarity of an 
individual or due to some nervous disorder. 

Chromidrosis, colored sweat, is due to excretion of something taken 
into the stomach or to local bacterial infection. 

Sudamina is the eruption of tiny vesicles in the epidermis, due to 
blocking of sweat-gland ducts or their rupture as they pass through 
this layer. 

Inflammation of the sweat-glands is known as hydradenitis. 

Cysts and adenomata sometimes arise in sweat-glands. 

HAIR 

Hypertrichosis is excess of hair, and may be congenital or due to 
irritation. 

Alopecia is congenital absence of hair, or its disappearance during 
life. In the acquired form it may occur without apparent cause as the 
result of atrophy of the skin, or following acute infection. In the form 
of alopecia areata hair disappears in sharply outlined patches, leaving 
the skin smooth, flat, and dry. It may spread until all parts are de- 
nuded. There is atrophy and slight cellular infiltration of the skin, 
and the pigment is decreased. 

Trichorrhexis is an unusual fragility of the hairs. 

Canities. — This name is given to loss of color of the hair in spots. 
It has as its cause, probably, a nervous disorder. Pigment is lacking 
and air is found in the shaft. 

NAILS 

The nails respond to slight injury by the appearance of white spots, 
probably due to air or small hemorrhages between the epithelial layers. 
Furrows across the nail occur after acute illness, or in delayed growth 
from any cause. Inflammation of the matrix (onychia) or its surround- 
ings (paronychia) is the result of causes similar to those given for derma- 
titis. It is commonest in syphilis and tuberculosis. Nails may be 
ribbed and distorted (onychogryphosis) , and penetrate the skin at the 
side, the so-called unguis incarnatus, or ingrowing nail. This may lead 
to inflammation or suppuration. 

Various inflammations — syphilis, favus, eczema — may involve the 
nail-bed. 

Tumors. — Fibroma, ecchondroma, and carcinoma may appear under 
the nails. 



INDEX 



Abdominal pregnancy, 805 
Abortion, tubal, 804 
Abrin, poisoning from, 34 
Abscess, 133 

alveolar, 602 

of brain, 913 

of liver, 662 

of lung, 564 

of prostate, 824 

of spleen, 446 

of thyroid gland, 700 

of tonsils, 605 

of vulva, 808 

periappendiceal, 638 

perinephric, 725 

psoas, 869 

retropharyngeal, 603 
Acervuloma, 204 
Acervulus, 715 
Acetonuria, 760 
Achondroplasia, 837 
Achromatic substance, 893 
Acid intoxication, 42 
excessive, 42 
in man, 42 
etiology of, 42 
symptoms of, 43 
Acid-proof bacilli, 324 
Acne, pancreatic, 690 

rosacea, 1001 

vulgaris, 1000 
Acrania, 887 
Acromegaly, 841 
Actinomyces bovis, 341 
cultivation of, 342 
pathogenicity of, 343 

madurs, 346 
Actinomycosis, 148 

definition of, 341 

etiology of, 341-343 

of bones, 853 

of brain, 919 

of heart, 497 

of intestines, 648 

of liver, 672 

of lungs, 580 

of mouth, 600 

of muscles, 869 

of pericardium, 502 

of skin, 1003 

of thyroid, 705 

pathological anatomy of, 345 
physiology of, 346 



Addison's disease, 709 
Adenocarcinoma of mammary glands, 835 
Adenofibroma of uterus, 785 
Adenoids, 605 

Adenoma, appearance of, 216 
definition of, 215 
etiology of, 215 
nature of, 219 
of kidney, 744 
of fiver, 674 

of mammary glands, 833 

of pituitary body, 714 

of suprarenal bodies, 711 

of testicles, 822 

of thyroid gland, 705 

of uterus, 787 

of vulva, 809 

seats of, 216 

structure of, 216 
Adenomatous goiter, 702 
Adenomyoma of uterus, 785 
Adenosarcoma of testicles, 822 
Adhesions, formation of, 138 
Adipose tissue, regeneration of, 154 
Age in carcinoma, 221 

in disease, 19 
Agglutination, bacterial, 265 

in typhoid fever, 292 
Air-embolism, 64 
Albinism, 974, 993 
Albuminoid degenerations, 85 
Albuminuria, 761 
Albumosuria, 761 

Bence-Jones, 762 
Alexin theory of immunity, 256 
Alkaptonuria, 760 
Alopecia, 1008 

areata, 1008 
a-granules, 417 
Alveolar abscess, 602 

angiosarcoma, 201 

sarcoma, 194 
Amebic dysentery, 640 
Amitosis, 150 
Amnion, 810 
Amyelia, 933 

Amylaceous bodies of prostate, 825 
Amyloid degeneration of muscles, 868 
formations, local, 93 
infiltration, 91 
definition of, 91 
etiology of, 92 

microscopical appearances of, 93 



64 



1009 



1010 



INDEX 



Amyloid infiltration of heart, 482 

of kidneys, 739 

of liver, 661 

of lymph-glands, 453 

of mucosa of intestines, 631 

of pancreas, 686 

of pericardium, 504 

of pituitary body, 714 

of spleen, 448 

of stomach, 620 

of suprarenal bodies, 709 

pathological anatomy of, 92 
physiology of, 94 

reactions for, 93 

seats of, 93 
Amyloidosis, 91 
Anal fissure, 634 
Anaphylaxis, 270 

Anaphylotoxin theory of infection, Fried- 

berger's, 271 
Anatomy, morbid, 17 

pathological, 17 
Anemia, 431 

aplastic, 437 

definition of, 431 

hemolytic ictero-, 438 

local, 58 

of brain, 902 

of bronchi, 532 

of conjunctiva, 965 

of esophagus, 609 

of heart-muscle, 481 

of kidneys, 718 

of larynx, 527 

of liver, 654 

of lungs, 538 

of mouth, 594 

of muscles, 863 

of pharynx, 602 

of pia-arachnoid, 874 

of retina, 978 

of skin, 993 

of spinal cord, 937 

of stomach, 613 

progressive pernicious, 435 

splenic, 444, 447 
Anemias, classification of, 431 

primary, 433 

secondary, 431 
etiology of, 431 
pathological anatomy of, 432 
physiology of, 433 
Anencephaly, 890 
Aneurysm, 511 

conditions in other parts associated 
with, 516 

definition of, 511 

dissecting, 515 

ectatic, 513 

etiology of, 512 

false, 517 

miliary, 513 

of arteries of brain, 901 

of heart, 496 

pathological anatomy of, 513 
saccular, 514 



Aneurysm, spurious, 517 
Angina, herpetic, 603. See also Pharyn- 
gitis. 

Ludwig's, 608 

pectoris, 492 

Vincent's, 340, 607 
Angioma, 181 

cavernous, 991 

of bones, 853 
Angioneurotic edema, 74 
Angiosarcoma, 200 

of brain, 921 
Angiosclerosis, 507 
Anguillula intestinalis, 400 

stercoralis, 400 
Anhydremia, 425 
Anidrosis, 1007 

Animal parasites, diseases from, 364 
in kidneys, 747 

transmission of disease, 410 
Aniridia, 974 
Anisocytosis, 420 
Ankyloglossia, 594 
Ankylosis of joints, 855 
Ankylostoma duodenale, 397 
Anlage, Baumgarten's, 19 
Annelides, 405 
Anophthalmia, 965 
Anteflexion of uterus, 772 
Anteversion of uterus, 772 
Anthracosis, 100, 562 
Anthrax, 1001 

definition of, 308 

etiology of, 308 

mode of infection in, 309 

of intestines, 648 

of muscles, 869 

pathological anatomy of, 310 
physiology of, 310 
Antibacterial immunity, 269 
Antigens, chemistry of, 272 
Antitoxic immunity, 268 
Antitoxin, action of, 261 

elimination of, 262 

transmission of, 261 
Anuria, 758 

Aorta, stenosis and atresia of, 469 
Aphthae, Bednar's, 595 
Aphthous stomatitis, 595 
Aplasia, 76 
Aplastic anemia, 437 
Apoplexia serosia, 904 
Apoplexy, 907 

Appendicitis, interstitial, 637 

obliterating, 638 

pathological anatomy of, 637 

relapsing, 638 

results of, 637 
Aqueduct of Sylvius, 884 
Arachnitis adhesiva, 930 
Arachnoid fluid, 924 
Arcus senilis, 972 
Argyria, 101 
Arsenic, action of, 33 
Arterial disorders, 57 
Arteries, 503 



INDEX 



1011 



Arteries, anatomical considerations of, 
503 

congenital defects of, 503 
of brain, aneurysms of, 901 
arteriosclerosis of, 900 
colloid degeneration of, 901 
hyaline degeneration of, 901 
syphilis of, 901 
syphilis of, 511 
tuberculosis of, 511 
Arteriocapillary fibrosis, 507 
Arterioliths, 72 
Arteriosclerosis, 507 

changes in other organs from, 510 
etiology of, 507 
in nephritis, 736 
of arteries of brain, 900 
pathogenesis of, 507 
pathological anatomy of, 508 
results from, 510 
Arteritis, acute, 505 
productive, 505 
suppurative, 505 
obliterating, 505 
proliferating, 505 
Arthritis, acute, 856 
atrophic, 859 
chronic, 856 
purulent, 857 
serous, 857 
deformans, 857 

clinical types of, 858 
etiology of, 859 
nomenclature of, 859 
dry, 859 
gonorrheal, 769 
gouty, 860 
hypertrophic, 859 
neuropathic, 860 
rheumatoid, 859 
Arthropoda, 405 
Ascaris cams, 395 

lumbricoides, 395 
Ascites, 692 
Asphyxia, 28 

Aspiration pneumonia, 554, 557 
Asthma, thymic, 712 
Astrocytes, 920 
Atavism, 21 

Ataxia, Friedreich's, 948 
Atelectasis, 546 

congenital, 546 

in later life, 547 ■ 
Atmospheric pressure, decreased, in 
etiology of disease, 28 
increased, in etiology of disease, 27 
Atrophic gastritis, 616 
Atrophy, brown, 77 

definition of, 76 

etiology of, 76 

numerical, 76 

of bone-marrow, 464 

of bones, 847 

of choroid, 977 

of glands of stomach, 620 

of heart, 493 



Atrophy of iris, 974 
of kidneys, 737 
of larynx, 529 
of liver, 657 

acute yellow, 659 

red, 657 
of lungs, 543 
of lymph-glands, 452 
of mammary glands, 830 
of mouth, 598 
of mucosa of intestines, 631 
of muscles, myopathic, 867 

neuropathic, 866 
secondary, 867 

progressive, 866 

pseudohypertrophic, 867 

simple, 867 
of nerves, 959 
of optic nerve, 982 
of pancreas, 685 
of pericardium, 504 
of prostate, 824 
of retina, 978 
of skin, 991 
of spleen, 448 
of testicles, 817 
of tongue and cheeks, 598 
of uterus, 783 

pathological anatomy of, 76 
physiology of, 77 

progressive spinal muscular, 951 

simple, 76 
Auricular septum, defects of, 469 
Auriculitis, purulent, 985 
Auriculoventricular orifices, stenosis and 

atresia of, 469 
Auto-intoxication, 24 
Autolysis in cellular necrosis, 116 
Autonomous new growths, 159 



Bacillary dysentery, 639 
Bacillus, 243 

aerogenes capsulatus, 312 

coli communis, cultivation of, 296 

distribution of, 296 

morphology of, 296 

pathogenicity of, 296 

pathological physiology of, 297 

synonyms of 295 
fusiformis, 340 
icteroides, 351 
cedematis maligni, 311 
of Ducrey and TJnna, 302 
of dysentery, 297 
proteus, 351 
pyocyaneus, 329 
smegma, 324 
tetani, 306 

tuberculosis, artificial culture of, 315 
avian, 315 
bovine, 315 
demonstration of, 316 
distribution of, 317 
human, 314 

modes of infection in, 317 



1012 



INDEX 



Bacillus typhi abdominalis, 289 
Bacteria, action of, 241 
biology of, 245 

chemical conditions of growth, 246 
chemistry of, 245 
chromogenesis of, 251 
classification of, 241 

of diseases from, 37 
diseases due to, 273 
effect of heat on, 246 

of light on, 246 

of toxic products of, 251 
fate of toxins of, 250 
ferments of, 247 
functions of, 247 
higher, diseases due to, 341 
in etiology of disease, 37 
involution forms of, 245 
local effects of, 251 
mechanical conditions of growth, 246 
morphology of, 243 
nature of, 241 

not causing specific infection, 349 

physical conditions of growth, 246 

products of, 247 

in culture-medium, 250 

proteins of, 247 

toxalbumins of, 249 

toxins of, 249 
Bacteriaceae, 242 
Bacterial agglutination, 265 
theory of immunity, 259 

immunity, 265 

toxins, poisoning from, 34 
Bacteriolysis, bacterial immunity as ap- 
plied to, 266 
Bacteriolytic theory of immunity, 257 
Bacterium anthracis, 308 

diphtheria, 285 

mucosum capsulatum group, 329 
pestis, 300 

pneumoniae of Friedlander, 283 

rhinoscleromatis, 304 
Bacteriuria, 763 
Balanitis, 814 
Balantidium coli, 379 
Banti's disease, 448 
Basophiles, 416 
Baumgarten's anlage, 19 
Bednar's aphthae, 595 
Beggiatoaceae, 242 
Bence-Jones albumosuria, 762 
Beriberi, 359 

Bile-ducts, dilatation of, 681 

stenosis of, 680 
Biliary cirrhosis, 668 
obstructive, 669 
ducts, inflammation of, 678. See also 
Cholangitis. 
Bilirubin in urine, 766 
Black tongue, 598 
Bladder, calculi in, 755 
results of, 755 
carcinoma of, 758 
changes of position of, 752 
exstrophy, 752 



Bladder, flbro-adenoma of, 758 
fibroma of, 758 
foreign bodies in, 755 
hemorrhage of, 753 
hyperemia of, 753 

inflammation of, 753. See also Cystitis. 

malformations of, 752 

myoma of, 758 

myxoma of, 758 

papilloma of, 757 

polypoid outgrowths of, 757 

rupture of, 753 

syphilis of, 755 

tuberculosis of, 755 
Blastomycosis, 348, 1004 
Blebs, 995 
Bleeders, 62 
Blepharitis, 983 
Blood, alterations in, 68 

anatomy of, 412 

changes in, 57 

character of, in leukocytosis, 429 
crises, 421 
diseases of, 412 

disturbances of circulation of, 56 

foreign bodies in, 442 

formation of, 419 

in leukemia, 440 

parasites in, 442 

plasma of, 419 
Blood-current, alterations in, 68 
Blood-plaques, 419 
Blood-platelets, 419 
Blood-poisons, poisoning from, 35 
Blood-vessel walls, changes in, 68 
Bone-marrow, 462 

atrophy of, 464 

chloroma of, 466 

fatty infiltration of, 463 

hypertrophy of, 464 

in leukemia, 464 

inflammation of, 465 

mucoid degeneration of, 464 

myeloma of, 466 

necrosis of, 464 

pigmentation of, 464 

tumors of, 466 
Bone-sand, 850 
Bones, actinomycosis of, 853 

anatomy of, 836 

angioma of, 853 

atrophy of, 847 

carcinoma of, 854 

caries of, 846 

chloroma of, 854 

chondroma of, 853 

cold abscesses of, 850 

comminuted fracture of, 839 

compound fracture of, 839 

cysts of, 854 

development of, 836 

diseases of, 836 

disorders of development of, 836 
enostoses of, 853 
exostoses of, 853 
fibroma of, 853 



INDEX 



1013 



Bones, giant growth of, 841 
hemorrhage from, 841 
hyperemia of, 841 
hypertrophy of, 841 
hypoplasia of, 847 
intermediary callus of, 840 
lepra of, 853 
lipoma of, 853 
myelogenous callus of, 840 
myeloma of, 854 
myxoma of, 853 

necrosis of, conditions associated with, 
847 

definition of, 846 

pathological anatomy of, 846 
osteoma of, 853 
parasites of, 854 
periosteal callus of, 840 
regeneration of, 153, 839 
sarcoma of, 853 

osteoid, 854 

secondary, 854 
sequestrum of, 846 
syphilis of, 851 

conditions associated with, 853 

congenital, 852 

etiology of, 852 

pathological anatomy of, 852 
syphilitic gumma of, 852 
thrombosis of, 841 
tuberculosis of, 849 

conditions associated with, 851 

etiology of, 849 

pathological anatomy of, 849 

seats of, 851 
tuberculous abscesses of, 850 
Bordet-Gengou bacillus of whooping- 
cough, 299 
Bothriocephalus mansoni, 394 
Bovine tuberculosis, 318 
Bow-legs, 855 

Brain, abnormalities in size of, 888 
abscess of, 913 
actinomycosis of, 919 
anatomy of, 882, 883 
anemia of, 902 
angiosarcoma of, 921 
arteries of, 900. See also Arteries of 

brain. 
carcinoma of, 922 
circulatory disturbances of, 902 
compression of, 918 
concussion of, 917 
congenital abnormalities of, 887 
development of, 882 
diseases of, 870 
edema of, 904 
embolism of, 908 
fibroma of, 921 
fissures of, 883 

ganglionar neuroglioma of, 920 
glioma of, 919 
hyperemia of, 903 
hypertrophy of, 889 
hypoplasia of, 889 
lacerated wounds of, 917 



Brain, lymphangioma of, 921 
osteoma of, 922 
partial absence of, 890 
perithelioma of, 921 
physiology of, 885 

postmortem degenerative conditions of, 

886 

psammoma of, 922 
punctate wounds of, 918 
red softening of, 909 
sarcoma of, 920 
sclerosis of, atrophic, 899 
diffuse, 899 
disseminated, 915 
hypertrophic nodular, 900 
lobar, 914 
multiple, 915 
secondary degeneration after hemor- 
rhage of, 907 
syphilis of, 919 
thrombosis of, 908 
total absence of, 890 
tuberculosis of, 918 
tumors of, 919 
white softening of, 909 
yellow softening of, 909 
Brain-sand, 715 
Bread-and-butter pleurisy, 588 
Bright's disease, acute, 722 
Brill's disease, 355 
Bromidrosis, 1008 

Bronchi, anatomical considerations of, 
531 

anemia of, 532 

congenital malformations of, 532 

dilatation of, 535 

foreign bodies in, 537 

hemorrhage of, 532 

hyperemia of, 532 

inflammation of, 532 

obstruction of, 534 

parasites of, 537 

stenosis of, 534 

syphilis of, 536 

tuberculosis of, 536 

tumors of, 536 

ulcers of, 534 
Bronchiectasis, 535 
Bronchiolectasis, 536 
Bronchiolitis, 556 

exudativa, 534 
Bronchitis, acute catarrhal, 532 

chronic catarrhal, 533 

fibrinous, 533 
Bronchogenic purulent pneumonia, 563 

tuberculosis, 567 
Bronchopneumonia, catarrhal, etiology 
of, 553 

pathological anatomy of, 554 

simple, 554 
Brown atrophy, 77 
Bubo, 769 

Bubonic plague, definition of, 300 
etiology of, 300 
pathological anatomy of, 301 
physiology of, 302 



1014 



INDEX 



Bullae, 995 

Burdach, column of, 884, 932 
Bursa?, inflammation of, 862 
Bursitis, 862 



Cachexia strumipriva, 706 
Caisson disease, 27 

Calcareous infiltration of pericardium, 
504 

of pia-arachnoid, 929 
Calcicosis, 100 
Calcification, 96 

definition of, 96 

etiology of, 96 

of choroid plexus, 923 

of kidneys, 739 

of lymph-glands, 453 

of muscles, 868 

of spleen, 449 

of stomach, 620 

of testicles, 817 

of veins, 518 

pathological anatomy of, 96 
physiology of, 98 

seats of, 97 
Calculi in pelvis of kidney, 749 

mulberry, 756 

pancreatic, 690 
Calculus of bladder, 755 
Callosity, 991 
Callus, intermediary, 840 

myelogenous, 840 

periosteal, 840 
Cancer en cuirasse, 835, 1006> 

special forms of, 230 
Canities, 1008 

Carbohydrate metabolism, diseases of, 47 
Carbonates in urine, 766 
Carbuncles, 135, 1001 
Carcinoma, age in, 221 

appearance of, 221 

basocellulare, 1006 

congenital theory of, 220 

definition of, 219 

degenerative changes in, 225 

dyscrasia in, 221 

etiology of, 219 

glandular, 229 

heredity in, 221 

infectious theory of, 220 

lenticular, of skin, 1006 

nature of, 226 

of bladder, 758 

of bones, 854 

of brain, 922 

of ductless glands, 711 

of Fallopian tubes, 802 

of intestines, 649 

of kidney, 744 

of larynx, 530 

of liver, 675 

of lungs, 581 

of lymphatic glands, 462 

of mammary glands, 833 

of ovaries, 796 



Carcinoma of pancreas, 689, 698 
of penis, 815 
of prostate, 828 
of spinal cord, 957 
of spleen, 449 
of stomach, 623 

pathological physiology of, 625 

varieties of, 624 
of testicles, 822 
of thyroid gland, 705 
of urethra, 770 
of uterus, 788 
of vagina, 807 
of vulva, 809 

pathological physiology of, 226 

seats of, 222 

structure of, 223 

traumatic theory of, 220 

varieties of, 227 
Cardioliths, 72 
Caries of bones, 846 

of teeth, 601 
Cartilage, regeneration of, 153 
Caruncle of vulva, 809 
Caseation, 110 

of testicles, 817 
Casts, blood-, 734 

cellular, 734 

crystalline, 734 

fatty, 735 

granular, 735 

hyaline, 734 

leukocvtic, 734 

tube-, 733 

waxy, 734 
Cataract, capsular, 973 

lenticular, 973 
Catarrh, acute nasal, 525 

spring, 966 
Catarrhal bronchopneumonia, 553 

enteritis, 633 

inflammation, 135 

jaundice, 635, 684 

pharyngitis, 602 

stomatitis, 595 
Caustics, action of, 31 
Cavity formation in lungs, 572 
Cecitis, 636 

Cecum, inflammation of, 636 
Cell contents, 243 
division, direct, 150 
epithelioid, 141 
irritation, 416 
multiplication, 150 
plasma, 416 
spider, 885 
stimulation, 416 
Cell-membrane, 244 
Cellular necrosis, alterations in 
nuclei in, 114 
in form of cell in, 114' 
autolysis in, 116 
circulatory phenomena in, 116 
etiology of, 114 
general pathology of, 114 
karyolysis in, 114 



INDEX 



1015 



Cellular necrosis, karyorrhexis in, 114 
pathological anatomy of, 114 
postmortem alterations in, 115 
degeneration of tissues, 116 
Cellulitis, 1002 
Cephalhematoma, 842 

internal, 870 
Cercomonas coli hominis, 367 

hominis, 366 
Cerebellum, anatomy of, 884 

hypoplasia of, 889 
Cerebral hemispheres, hypoplasia of, 889 
Cerebrospinal fluid, 924 
hypersecretion of, 922 
in disease, 925 

meningitis, epidemic, 877 
Cervix, chronic endometritis of, 778 

hypertrophy of, 783 

phagedenic ulceration of, 780 

syphilis of, 782 
Cestodes, 384 
Chalazion, 983 
Chalicosis, 562 
Chancre, 336 

of penis, 815 

of syphilis, 146 

soft, 302 
Chancroid, 815 

of vulva, 809 
Cheesy pneumonia, 558. See also 

Tuberculous pneumonia. 
Chemistrv, pathological, 17 
Chemotaxis, 122 
Chilblain, 27 

Chlamydobacteriaceae, 242 
Chlamydozoa, 363 
Chloasma, 993 
Chloroma, 188 

of bone, 854 

of bone-marrow, 466 
Chlorosis, 433 

definition of, 433 

etiology of, 434 

pathological anatomy of, 434 
physiology of, 435 
Choked disk, 981 
Cholangitis, 678 

chronic, 679 

results of, 680 

suppurative, 679 
Cholecystitis, 680 
Cholelithiasis, 681 
Cholera, 330, 640 

causes of, 332 

conditions associated with, 642 
definition of, 330 
etiology of, 330 

pathological anatomy of, 332, 640 
physiology of, 332 
Cholesteatoma, 237 

of middle ear, 989 

of pia-arachnoid, 881 
Cholesterin deposits, 99 

in urine, 766 
Choluria, 760 

Chondrocarcinoma of testicles, 823 



Chondrodystrophia fetalis, 837 
Chondroma, appearance of, 176 
definition of, 176 
etiology of, 176 
nature of, 178 
of bones, 853 
of mammary glands, 832 
of testicles, 822 
seats of, 177 
structure of, 177 
Chorion, 810 
Choroid, 965, 977 
atrophy of, 977 
hemorrhage in, 977 
plexus, 922 

calcification of, 923 
hemorrhage into, 923 
inflammation of, 922 
pigmentary infiltration of, 923 
tuberculosis of, 923 
tumors of, 923 
ruptures of, 977 
syphilis of, 978 
tuberculosis of, 978 
tumors of, 978 
wounds of, 977 
Choroiditis, 977 
Chromidrosis, 1008 
Chromogenesis of bacteria, 251 
Chyluria. 763 
Ciliary body, 965, 976 
atrophy of, 976 
cysts of, 977 
syphilis of, 977 
tuberculosis of, 977 
Circulation of blood, disturbances of, 56 
Circulatory system, diseases of, 467 
Cirrhosis, biliary, 668 
Hanot's. 669 
Laennec's, 665 
of liver, 663 
of pancreas, 688 
pigmentary, 670 
portal, 665 
Clap-threads, 769 
Cleft palate, 594 
Clitoris, elephantiasis of, 807 
Cloud y swelling, 79 
definition of, 78 
etiology of, 78 
of kidneys, 737 
pathological anatomy of, 78 

physiology of, 79 
seats of, 79 
Club-foot, 855 
Coagulating ferment, 248 
Coagulation necrosis, 107 
definition of, 107 
etiology of, 107 
morbid physiology of, 108 
of muscles, 868 
pathological anatomy of, 107 
Coccaceae, 242 
Cocci, diseases due to, 273 
Coccidia, 377 
Coccidioides immitis, 348 



1016 



INDEX 



Coccidiosis, 348 
Coccidium bigeminum, 378 

cuniculi, 377 
Coccus, 243 

Cohnheim's emigration theory of inflam- 
mation, 118 . 
theory of tumor, 160 
Cold in etiology of disease, 26 
Colitis, 639 

mucous, 639 
Colloid degeneration, 90 
definition of, 90 
etiology of, 90 

microscopical appearance of, 90 
of arteries of brain, 901 
of pituitary body, 714 
pathological anatomy of, 90 
physiology of, 91 
goiter, 701 
Coloboma, 965, 974 
Colpitis, 806. See also Vaginitis. 
Column of Burdach, 932 

of Gowers, anterolateral, 932 
Columns of Goll and Burdach, 884 
Comedo, 1007 
Commotio cerebri, 25 
Communicable disease, 38 

methods of communication, 407 
Complement deviation, 269 

fixation, 269 
Compression of brain, 918 
Concrements, 99 

Concretions in uriniferous tubules, 740 

prostatic, 825 
Concussion of brain, 917 
Condyloma, 992 

acuminatum of penis, 815 

latum of syphilis, 146 
Congenital pneumonia, syphilitic, 563 

syphilis, 338 

theory of carcinoma, 220 
Congestion of lungs, 538 

passive, of esophagus, 609 
Conglutination, 69 
Conjunctiva, 964, 965 

anemia of, 965 

edema of, 966 

hemorrhage of, 966 

hyperemia of, 966 

syphilis of, 969 

tuberculosis of, 969 
Conjunctivitis, acute catarrhal, 966 

angular, 968 

follicular, 967 

Parinaud's, 968 

phlyctenular, 968 

pseudomembranous, 966 

purulent, 768 

vernal, 966 
Consumption, galloping, 569 
Contact infection, 408 
Contagious disease, 37 
Contre-coup, hemorrhage by, 917 
Cor bovinum, 495 

villosum, 500 
Cord, abnormal smallness of, 933 



Cord, anatomy of, 882 

development of, 882 
Corectopia, 974 
Corium, 990 

inflammation of, 1001 
Cornea, 964, 970 

leprosy of, 972 

ring abscess of, 972 

syphilis of, 972 

tuberculosis of, 972 

wounds of, 972 
Corns, 991 

Coronary artery, embolism of, 472 

thrombosis of, 472 
Corpora amylacea, 92 
Corpus callosum, 883 

fibrosum, 791 

luteum, 791 
Corpuscles, alteration of isotonicity of, 
422 

dust-, 421 

red, 413 

diapedesis of, in inflammation, 123 

shadow, 421 

white, 414 
Cowper's glands, 828 
Cranioschisis, 888 
Craniotabes, 838 
Cretinism, 706 
Croup, false, 527 
Croupous enteritis, 633 

laryngitis, 528 

pneumonia, 280, 549. See also Fibrin- 
ous pneumonia. 
definition of, 280 
etiology of, 280 

Crusts, skin, 995 

Cryptophthalmia, 965 

Cryptorchismus, 817 

Crystalline lens, 973 
dislocation of, 974 

Currant-jelly clots, 471 

Cutaneous horns, 991 

Cutis, 990 

Cyanosis, 59 

chronic, with polycythemia and en- 
larged spleen, 428 

Cyclencephaly, 888 

Cyclopia, 965 

Cylindrical epithelioma, 229 
Cylindroids, 735 
Cylindroma, 202 

Cystadenoma of mammary glands, 833 
Cystic accumulations in lesser omental 

cavity, 690 
Cystin in urine, 766 
Cystinuria, 762 
Cystitis, 753 

chronic, 754 

mucopurulent, 754 

phlegmonous, 754 

pseudomembranous, 754 
Cystocele, 773 

vaginal, 805 
Cystoma of ovaries, 793 

papilliferous, of testicles, 823 



INDEX 



1017 



Cystosarcoma of mammary glands, 833 
Cysts, classification of, 231 

definition of, 231 

dermoid, 236 

epithelial, 232 

of bones, 854 

of ciliary body, 977 

of cornea, 972 

of dura mater, 873 

of- eye, 969 

of Fallopian tubes, 802 
of iris, 976 
of kidneys, 745 
of Kobelt's tubes, 797 
of liver, 677 
of lungs, 584 
of mammary glands, 835 
of pancreas, 689 
of parovarium, 796 
of penis, 816 
of pituitary body, 714 
of prostate, 828 
of spleen, 449 
of testicles, 823 
of urethra, 770 
of uterus, 790 
of vagina, 807 
of vulva, 809 
proliferation, 232 
retention, 232 
sebaceous, 1007 
softening, 232 
tubo-ovarian, 802 
Cytolysin, 268 

Cytolysis, bacterial immunity as applied 
to, 266 



Dacryo-adenitis, 970 
Dacryo-cystitis, 970 
Daughter stars, 151 
Davainea madagascariensis, 390 
Decidua, 810 

reflexa, 810 

serotina, 810 

vera, 810 
Decubitus, 993 
Degeneration, albuminoid, 85 

colloid, 90 

fatty, 82 

hyaline, 85 

mucoid, 88 

of intracardiac ganglia, 485 
of mouth, 598 
of nerves, 959 

of spinal cord, secondary, 953 

so-called, 78 
Degenerative inflammation, 137 
Deglutition pneumonia, 554 
^-granules, 417 
Dengue, 360 

Dermacentor occidentalis, 362 
Dermatitis, 994 
Dermatographia, 994 
Dermatornycosis, 349 
Dermatomyositis, 864 



Dermoid cyst, 236 
of ovaries, 795 
of testicles, 823 
Dextrinuria, 759 
Diabete bronze, 52, 102 
Diabetes mellitus, 49 
etiology of, 49 
metabolism in, 51 
pathogenesis, 50 
pathological anatomy of, 52 
Diaceturia, 760 
Diapedesis, 61 

of red corpuscles in inflammation, 123 
Diastatic ferments, 248 
Diastematomyelia, 933 
Dibothriocephalus cordatus, 394 
latus, 393 

geographical distribution, 394 
Dicrocoelium lanceatum, 381 
Dilatation of bile-ducts, 681 
of bronchi, 535 
of esophagus, 611 
of Fallopian tubes, 798 
of heart, 494 
of intestines, 627 
of lymphatic vessels, 521 
of stomach, 621 

atonic, 621 
of ureter, 748 
of uterus, 775 
of veins, 519 
Diphtheria, definition of, 285 
distribution of bacilli in, 287 
etiology of, 285 
internal lesions in, 287 
mixed infection in, 286 
of animals, 287 
of pharynx, 606 
of vulva, 809 

pathological anatomy of, 287 
physiology of, 288 

predisposing causes of, 286 
Diphtheria-like bacilli, 288 
Diphtheritic inflammation, 131 

laryngitis, 528 

rhinitis, 525 

salpingitis, 800 
Diplococcus pneumonia 1 , 280, 549 

in other diseases, 282 
Diplogonoporus grandis, 394 
Dipylidium caninum, 390 
Direct infection, 408 
Disease, age in, 19 

cold in, 20 

conditions of life in, 20 
definition of, 17 
determining causes of, 23 
etiology, 19 
foot-and-mouth, 362 
heat in, 20 
idiosyncrasy in, 20 
injury in, 20 
nutrition in, 20 
pathologic disposition to, 20 
physical forces in, 20 
poisons in, 20 



1018 



INDEX 



Disease, predisposing factors, 19 
race in, 20 
sex in, 20 
symptoms of, 18 
transmission of, by animals, 410 

by food, 409 

by human beings, 410 

by insects, 409 

by soil, 409 

by unknown methods, 411 

by water, 409 

indirect, 409 
Diseases, animal parasites from, 364 
communicable, methods of transmis- 
sion, 407 
due to bacillary forms, 285 

to bacteria, 273 

to cocci, 273 

to higher bacteria, 341 

to spirilla, 330 

to spirochetes, 334 
hemorrhagic, 349 
infectious, of unknown origin, 351 
of blood, 412 
suppurative, 273 
Dissecting aneurysm, 515 
Distomum haematobium, 382 

hepaticum, 380 
Diverticula of esophagus, 611 
Dropsical infiltration, 95 

of liver, 661 
Dropsy of joints, 856 
of peritoneum, 692 
Ductless glands, carcinoma of, 711 

diseases of, 699 
Ductus Botalli, patulous, 470 
Dumdum fever, 370 
Duodenitis, 635 
Dura mater, cysts of, 873 

fatty infiltration of, 928 

hemorrhage from, 870, 928 

sarcoma of, 929 

sinus thrombosis of, 870 

syphilis of, 872, 929 

tuberculosis of, 872 

tumors of, 872, 929 
Dust-cells, 560 
Dust-corpuscles, 421 
Dust-embolism, 64 
Dyscoria, 974 

Dyscrasia, constitutional, 159 

in carcinoma, 221 
Dysentery, 639 

amebic, 640 

bacillary, 639 

bacillus of, 297 
Dysmenorrhea membranacea, 776 
Dyspepsia, 616 



Ear, 984 

anatomy of, 984 
congenital defects of, 985 
external, 985 

frost-bite of, 985 

mycosis of, 986 



Ear, external, syphilis of, 986 
tuberculosis of, 986 
tumors of, 986 
internal, circulatory disturbances of, 
989 

inflammation of, 989 
middle, cholesteatoma of, 989 

hemorrhage of, 987 

hyperemia of, 987 

syphilis of, 988 

tuberculosis of, 988 

tumors of, 989 
Ecchymosis, 63 
Echinococcus cysts, 391 

of testicles, 824 

seats of, 393 
Echinorhynchus gigas, 404 
Ectatic aneurysm, 513 
Ecthyma, 995 
Ectoplasm, 244 
Eczema, 997 

Edema, alterations of blood in, 74 

of tissue liquids in, 75 
angioneurotic, 74 
decreased tissue elasticity in, 73 
definition of, 72 
direct filtration in, 73 
etiology of, 72 
in inflammation, 125 
in nephritis, 736 
increased blood-pressure in, 73 

permeability of capillary walls in, 74 
malignant, 311 

obstruction of lymphatic circulation in, 
74 

of conjunctiva, 966 
of eyeiids, 983 
of kidneys, 719 
of larynx, 527 
of lungs, 540 

of mucosa of intestines, 632 

of nasal cavities, 524 

of nerves, 958 

of pharynx, 602 

of pia-arachnoid, 874 

of skin, 994 

of vulva, 808 

osmosis in, 73 

pathological anatomy of, 75 

results of, 75 
Edematous inflammation, 130 
Ehrlich's side-chain theory of immunity, 

262 

Eimeria hominis, 378 
Electrical influences in etiology of disease, 
29 

Elephantiasis, 992 

of clitoris, 807 

of labia;, 807 

of scrotum, 815 

of vulva, 809 
Emboli, sources and nature of, 64 
Embolism, 64 

dust-, 64 

fat-, 64 

infectious, 67 



INDEX 



Embolism of arteries of muscles, 863 
of brain, 908 
of coronary artery, 472 
of lungs, 542 

of mesenteric arteries, 632 

of portal vein, 656 

of renal arteries, 719 

of spermatic artery, 818 

of splenic artery, 445 

paradoxical, 65 

results of, 65 

retrograde, 65 

seats of, 64 
Emigration of leukocytes, 61 
Emphysema, infectious, 312 

of lungs, atrophic, 545 
bullous, 545 
interstitial, 543 
vesicular, 544 
vicarious, 544 

senile, 546 
Empyema of gall-bladder, 680 

purulent, 589 
Encephalitis, 910 

acute parenchymatous, 911 

chronic, 914 

primary acute hemorrhagic, 914 
simple acute focal, 911 
suppurative, 912 
Encephalocele, 888 
Encephalomalacia, 909 
End-arteries, 66 
Endarteritis, 505 

chronica deformans, 507 
Endemic disease, 38 
Endocarditis, acute, 473 

changes in other organs in, 479 
etiology of, 473 
lesions in other organs in, 477 
pathological anatomy of, 474 
results of, 476 
chronic, 477 

changes in heart in, 478 
etiology of, 477 
malignant, 477 
pathological anatomy of, 477 
pathological physiology of, 479 
recurrent, 477 
subacute, 477 
Endocardium, diseases of, 472 

inflammation of, 473 
Endometritis, 777 
acute catarrhal, 777 
chronic, 777 

of cervix, 778 
decidualis, 811 
exfoliativa, 776 
glandularis, 777 
interstitialis, 777 
Endoplasm, 244 
Endosporium, 244 
Endothelioma, 203 

of lymphatic glands, 462 
of pia-arachnoid, 880 
of spleen, 449 
Enophthalmos, 983 



Enostoses of bones, 853 
Entamoeba buccalis, 366 

histolytica, 640 
description of, 364 
pathogenesis of, 366 

urinalis, 366 
Enteritis, catarrhal, 633 

chronic, 635 

croupous, 633 

follicular, 633, 635 

pathological physiology of, 635 

pseudomembranous, 634 

suppurative, 634 

toxic, 633 

ulcerative, 634 
Enterocystoma of intestines, 627 
Enterogenic albumosuria, 761 
Enteroliths, 653 

Enteromycosis of intestines, 648 
Enterorrhagia, 63 
Enzymes, 247 
Eosinophile granules, 417 
Eosinophils, 416 
Epencephalon, 883 
Ependymitis of ventricles, 923 
Epicanthus, 965 
Epidemic disease, 38 
Epidermis, 990 
Epididymitis, 818 
acute, 768, 819 
Epiphysis cerebri, 715 
Episcleritis, 972 
Epispadias, 814 
Epistaxis, 63, 524 

Epithelial cysts, appearance of, 232 
definition of, 232 
etiology of, 232 
nature of, 234 
seats of, 233 
structure of, 233 
tumors, 212 
Epithelioid cells, 141 
Epithelioma adenoides, 991 
contagiosum, 1005 
cylindrical, 229 
of penis, 815 

of skin, benign cystic, 1006 

squamous, 227 
of skin, 1006 
Epithelium, regeneration of, 151 
e-granules, 418 
Epulis, 196, 600 
Ergot, poisoning from, 34 
Erosions of uterus, 779 
Erysipelas, 1002 
Erythema, 995 
Erythrasma, 1004 
Erythroblasts, 421 

primitive, 419 
Erythrocytes, 413 

nucleated, 421 

skeined, 414 
Escharotics, action of, 31 
Esophagitis, catarrhal, 610 
chronic, 610 

phlegmonous. 610 



1020 



INDEX 



Esophagitis, pseudomembranous, 610 

ulcerative, 610 
Esophagomalacia, 612 
Esophagus, 609 

anemia of, 609 

congenital defects of, 609 

dilatation of, 611 

diverticula of, 611 

hyperemia of, 609 

inflammation of, 610 

passive congestion of, 609 

perforation of, 611 

rupture of, 611 

stenosis of, 610 

syphilis of, 612 

tuberculosis of, 612 

tumors of, 612 

typhoid ulceration of, 612 
Etat crible, 910 
Ethylendiamin, 37 
Etiology, definition of, 17 

of disease, 19 
Eumycetes, 242 
Eunuchism, 816 

Eustachian tube, inflammation of, 989 
Eustrongylus gigas, 405 
Exophthalmos, 983 
Exosporium, 244 
Exostoses of bones, 853 
Exstrophy of bladder, 752 
Extra-uterine pregnancy, 803 
etiology of, 803 
pathological anatomy of, 803 
varieties of, 803 
Eye, anatomy of, 964 
anterior chamber of, 972 
cysts of, 969 
tumors of, 969 
Eyelids, 983 
edema of, 983 
ptosis of, 983 

congenital, 965 
tumors of, 983 



Fallopian tubes, anatomy of, 797 

carcinoma of, 802 

changes of position of, 797 

congenital abnormalities of, 797 

cysts of, 802 

development of, 797 

dilatation of, 798 

fibroma of, 802 

fibromyoma of, 802 

hematoma of, 798 

hemorrhages into, 798 

hyperemia of, 798 

lipoma of, 802 

sarcoma of, 802 

stenosis of, 798 

syncytioma malignum of, 802 

syphilis of, 802 

tuberculosis of, 801 
False aneurysm, 517 
Farcy, 305 

Fasciola hepatica, 380 



Fat crystals in urine, 766 
embolism, 64 
metabolism of, 40 
necrosis, 111 
of pancreas, 686 
Fat-splitting ferments, 248 
Fatty casts, 735 
degeneration, 82 
definition of, 82 
etiology of, 82 

microscopic appearances of, 83 

of heart, 483 

of kidneys, 738 

of liver, 659 

of muscles, 867 

of pericardium, 504 

of prostate, 825 

of stomach, 620 

of suprarenal bodies, 709 

of testicles, 817 

of uterus, 783 

of veins, 518 

pathological anatomy of, 83 

physiology of, 84 
seats of, 84 
infiltration, 80 
definition of, 80 
etiology of, 80 
of bone-marrow, 463 
of dura mater, 928 
of heart, 482 
of kidneys, 738 
of liver, 658 
of lymph-glands, 453 
of mammary glands, 831 
of muscles, 868 
pathological anatomy of, 81 

physiology of, 81 
seats of, 81 
Favus, 1004 

Ferment theory of immunity, 259 
Fermentation, 247 
Ferments, coagulating, 248 

diastatic, 248 

effects of, 249 

fat-splitting, 248 

hydrolytic, 248 

inverting, 248 

nitrifying, 248 

of bacteria, 247 

oxidizing, 248 

proteolytic, 248 
Fetal membranes, 810 

hemorrhage from, 810 
Fever, conservative effects of, 54, 55 

definition of, 53 

etiology of, 54 

nature of, 53 

paratyphoid, 646 

pathological anatomy of, 55 
physiology of, 55 

typhoid, 642 
Fibrin-ferment, 69 
Fibrinogen, 69 
Fibrinous bronchitis, 533 

inflammation, 131 



INDEX 



1021 



Fibrinous pleuritis, 587 

pneumonia, 549 
Fibrinuria, 762 

Fibro-adenoma of bladder, 758 

of mammary glands, 831 
Fibroid phthisis, 569, 573 
Fibroids of uterus, 784 
Fibroma, appearance of, 170 

definition of, 169 

etiology of, 169 

intracanalicular, 171 

nature of, 172 

of bladder, 758 

of bones, 853 

of brain, 921 

of Fallopian tubes, S02 

of kidneys, 741 

of larynx, 530 

of mammary glands, 831 

of pancreas, 698 

of skin, 1005 

of testicles, 822 

of vagina, 807 

of vulva, 809 

seats of, 170 

secondary changes in, 172 

structure of, 171 
Fibromyoma of Fallopian tubes, 802 
Fibromyxoma of vulva, 809 
Fibrosis, arteriocapillary ; 507 

general, 138 
Fibrous connective tissue, regeneration 
of, 151 

pneumonia, 560 
Filaria bancrofti, 402 

medinensis, 401 
Filarise, varieties of, 404 
Filariasis, 404 
Filterable viruses, 351 
Fissure, anal, 634 
Fistula in ano, 639 
Flagella, 244 
Fleshy moles, 811 
Fluke-worms, 380, 384 
Focal necroses, 112 
Follicular cysts of ovaries, 793 

enteritis, 633 
Food, diminished supply of, 39 

increased supply of, 40 

transmission of disease, 409 
Foot-and-mouth disease, 362, 595 
Foreign bodies, cysts from, 232 
in bladder, 755 
in bronchi, 537 
in intestines, 652 
Foreign-body tubercle, 143 
Fowl tuberculosis, 325 
Fracture, comminuted, 839 

compound, 839 

definition of, 839 

repair of, 839 
Fragilitas ossium, 848 
Frambesia, 341 
Freckles, 993 

Friedberger's anaphylotoxin theory of in- 
fection, 271 



Friedreich's ataxia, 948 
Fungus, benign, of testicles, 819 

syphilitic, of testicles, 822 
Furuncles, 135, 1001 



Galactorrhea, 831 

Galen's definition of inflammation, 118 

Gall-bladder, contraction of, 681 

empyema of, 680 

inflammation of, 680 
Galloping consumption, 569 
Gall-stones, etiology of, 681 

pathological anatomy of, 682 

structure of, 682 
y-granules, 417 

Ganglia of spinal nerves, diseases of, 958 

of tendon-sheaths, 862 
Gangrene, 105, 112 

definition of, 112 

dry, 112 

moist, 113 

of lung, 565 

of vulva, 809 

primary, 112 

secondary, 112 
Gangrenous inflammation, 137 

stomatitis, 597 
Gastrectasia, 621 
Gastric ulcer, 617 
etiology of, 617 
pathological anatomy of, 618 
Gastritis, acute, 614 

atrophic, 616 

chronic, 615 

hypertrophic, 616 

interstitial, 616 

pathological physiology of, 616 

pseudomembranous, 614 

ulcerative, 615 
Gastro-intestinal tract, diseases of, 594 
Gastromalacia, 620 
Gastroptosis, 621 
Genu valgum, 855 

varum, 855 
Germinal cells, 882 
Giant growth of bones, 841 
Giant-celled sarcoma, 195 
Giant-cells, classification of, 128 

in inflammation, 125 

Langhans', 142 
Gigantism, 158 
Gin-drinkers' liver, 665 
Glanders, 148, 526 

definition of, 304 

etiology of, 304 

hemolymph, 451 

lymphatic, 450 

of larynx, 529 

of lungs, 579 

of muscles, 869 

of skin, 1003 

pathological anatomy of, 305 
physiology of, 305 
Glandular carcinoma, 229 
organs, regeneration of, 154 



1022 



INDEX 



Glans penis, inflammation of cavernous 
bodies of, 815 
of mucous membrane of, 814 
Glaucoma, 980 
Gleet, 769 

Glioma, appearance of, 205 
definition of, 205 
etiology of, 205 
ganglionare, 207 
appearance of, 208 
definition of, 207 
etiology of, 207 
nature of, 208 
structure of, 208 
nature of, 206 
of brain, 919 
of retina, 206 
of spinal cord, 957 
of suprarenal bodies, 711 
seats of, 205 
structure of, 206 
Gliosis, hypertrophic nodular, 888 
Glomerulonephritis, acute, 722 
Glossitis, 594, 598 
Glucosuria, alimentary, 48, 759 
causes of, 49 

from excessive hepatic glycolysis, 49 
renal, 51 
Glycogenic infiltration, 94 
definition of, 94 
etiology of, 94 
of kidneys, 739 
pathological anatomy of, 95 
physiology of, 95 
reaction, 423 
Glycolysis, excessive hepatic, glucosuria 

from, 49 
Goiter, adenomatous, 702 
colloid, 701 
cystic, 700 
etiology of, 700 
fibrous, 701 

mechanical effects of, 704 

parenchymatous, 700 

pathological anatomy of, 700 

secondary changes in, 704 

vascular, 701 
Goll, columns of, 884 
Gonococcus, 279 

cultivation of, 279 

pathogenicity of, 279 
Gonorrhea, 767 

definition of, 278 

etiology of, 278 

pathological anatomy of, 279 
physiology of, 280 
Gonorrheal arthritis, 769 

tenosynovitis, 769 

urethritis, 770 
Gout, 46, 860 

etiology of, 46 

pathogenesis of, 47 

pathological anatomy of, 46 
Gouty tophi, 860 

Gowers, anterolateral column of, 932 
Granular casts, 735 



Granular disintegration, 79 
Granulation tissue in inflammation, 128 
Granules of leukocytes, 417 
Granuloma, infectious, 141 

pyogenicum, 349 
Graves' disease, 707 
Grawitz, granular degeneration of, 26 
Gruber-Durham phenomenon in typhoid 

fever, 292 
Gumma, 1003 

of syphilis, 146 



Hair, 1008 

Hair-follicles, inflammation of, 1000 
Hanot's cirrhosis, 669 
Hansemann's theory of tumors, 161 
Harelip, 594 

Healing by first intention, 137 

by immediate union, 137 

by second intention, 138 
Heart, 467 

abnormality in size of, 468 
of position of, 468 

actinomycosis of , 497 

amyloid infiltration of, 482 

anatomical considerations of, 467 

aneurysm of, 496 

atrophy of, 493 

changes in, in chronic endocarditis, 478 
congenital diseases of, 468 
deformities of, 468 
development of, 467 

defective, 468 
dilatation of, 494 
fatty degeneration of, 483 

infiltration of, 482 
hyaline degeneration of, 482 
hypertrophy of, 494 
hypoplasia of, 492 
new-growths of, 497 
overaction of, 57 
parasites in, 498 

parenchymatous degeneration of, 481 

pathological physiology of, 470 

primary tumors of, 497 

rupture of, 497 

secondary tumors of, 497 

syphilis of, 497 

thrombosis of cavities of, 471 

tuberculosis of, 497 

valvular defects of, 470 

weak, 56 

wounds of, 497 
Heart-muscle, anemia of, 481 

hemorrhages in, 481 

hyperemia of, 481 

inflammation of, 486 

pathological physiology of, 486 

segmentation of fibers of, 485 
Heat in etiology of disease, 25 
Heberden's nodes, 859 
Hemangioma, appearance of, 182 

definition of, 182 

etiology of, 182 

nature of, 184 



INDEX 



1023 



Hemangioma, seats of, 182 

structure of, 183 
Hematemesis, 63 
Hematocele, retro-uterine, 776 
Hematochyluria, 763 
Hematocolpos, 805 
Hematogenic albumosuria, 762 

purulent pneumonia, 563 

tuberculosis, 575 
Hematogenous jaundice, 684 

pigmentation, 101 

microscopic appearance of, 103 
Hematoidin, 870 

in urine, 766 
Hematoma, 63 

auris, 985 

of Fallopian tubes, 798 

of muscles, 868 

of vulva, 808 
Hematometra, 775, 805 
Hematomyelia, 933, 938 
Hematosalpinx, 801 
Hematuria, 762 
Hemicrania, 888 
Hemochromatosis, 102 
Hemocytolysis, 426 
Hemoglobin in urine, 766 
Hemoglobinemia, 426 
Hemoglobinuria, 762 

paroxysmal, 763 
Hemokoniae, 421 
Hemolymph glands, 451 
Hemolysis, 112 
Hemolytic ictero-anemia, 438 
Hemopericardium, 498 
Hemophilia, 62 
Hemoptysis, 63 
Hemorrhage, 60 

by contre-coup, 917 

causes of, 62 

cerebral, 904 
massive, 905 
punctate, 904 

classification of, 63 

from bones, 841 

from diseases of blood-vessels, 62 

from dura mater, 928 

from fetal membranes, 810 

from increase of blood-pressure, 62 

from mammary glands, 829 

from ovaries, 791 

in chorioid, 977 

in heart-muscle, 481 

in muscles, 863 

in pia-arachnoid, 874 

in spleen, 445 

into choroid plexus, 923 

into Fallopian tubes, 798 

into joints, 856 

into skin, 994 

into vaginal walls, 806 

into vitreous humor, 974 

leukocytosis from, 429 

neuropathic, 62 

of bladder, 753 

of bronchi, 532 



Hemorrhage of conjunctiva, 966 

of dura mater, 870 

of intestines, 631 

of kidneys, 719 

of larynx, 527 

of lungs, 540 

of middle- ear, 987 

of mouth, 594 

of nasal cavities, 524 

of nerves, 958 

of pancreas, 685 

of pericardium, 498 

of peritoneum, 691 

of pharynx, 602 

of pia-arachnoid, 929 

of retina, 970 

of spinal cord, 937 

of stomach, 613 

of suprarenal bodies, 710 

of uterus, 776 

petechial, of pleura, 585 

results of, 63 

traumatic, 62 
Hemorrhagic diathesis, 62 

diseases, 349 

infarcts, 63 
of lungs, 541 

inflammation, 135 

pancreatitis, acute, 687 

pleuritis, 590 
Hemorrhoids, 632 
Hemosiderosis, 670 
Hemosporidia, 372 
Hemothorax, 585 
Hepatitis, 662 

interstitial, acute, 662 
chronic, 663 

parenchymatous, 662 
Hepatogenous pigmentation, 104 
Hereditary congenital pathological condi- 
tions, 22 
Heredity in carcinoma, 221 

in etiology of disease, 21. See also 
Inheritance. 

pathologic conditions of later life de- 
pending on, 22 
Hermaphroditism, 239, 814 
Hernia, etiology of, 627 

external, varieties of, 628 

internal, varieties of, 628 

of intestine, 627 

pathological anatomy of, 628 

strangulated, 629 
Herpes, 996 
Heterochromia, 974 

Heterotopia of gray matter of spinal cord, 

933 

Hippuric acid in urine, 765 
Histoplasmosis, 371 
Hives, 994 
Hob-nail liver, 665 
Hodgkin's disease, 441 

of lymphatic glands, 461 

of spleen, 449 
Hordeolum, 983 
Horseshoe-kidney, 717 



1024 



INDEX 



Human transmission of disease, 410 
Hutchinson's teeth, 339, 601 
Hyaline casts, 734 
degeneration, 85 

definition of, 85 

etiology of, 86 

of arteries of brain, 901 

of heart, 482 

of lymph-glands, 453 

of muscles, 868 

of pericardium, 504 

of spinal cord, 936 

of spleen, 448 

pathological anatomy of, 86 
physiology of, 88 

seats of, 87 
Hydatid moles, 813 
Hydatids of Morgagni, 802 
Hydradenitis, 1008 
Hydremia, 425 

Hydrocele funiculi cystica, 820 
spermatici, 820 

processus vaginalis, 820 

spermatica, 820 
Hydrocephalus, acquired, 927 

acute, 879 

acquired internal, 927 

chronic, 927 

external, 910, 927 

fetal, 888 

internus, congenital, 925 

partial, 927 
Hydrolytic ferments, 248 
Hydroma durse matris, 871 
Hydrometra, 775 
Hydromyelia, 933, 934 
Hydropericardium, 498 
Hydrops articulorum, 857 

e vacuo, 910 

omenti, 692 
Hydrorrhachus, 933 
Hydrorrhcea gravidarum, 811 
Hydrosalpinx, 801 
Hydrothionuria, 761 
Hydrothorax, 585 
Hygroma, 874 
Hymenolepis diminuta, 389 

nana, 389 
Hyperemia, active, 59 
of lungs, 538 

arterial, 59 

collateral, 59 

local, 59 

neuroparalytic, 59 
neurotonic, 59 
of bladder, 753 
of bones, 841 
of brain, 903 
of bronchi, 532 
of conjunctiva, 966 
of dura mater, 870 
of esophagus, 609 
of Fallopian tubes, 798 
of heart-muscle, 481 
of intestines, 631 
of joints, 856 



Hyperemia of kidneys, 718 
of larynx, 527 
of liver, 654 

of mammary glands, 829 

of middle ear, 987 

of mouth, 594 

of muscles, 863 

of nasal cavities, 524 

of ovaries, 791 

of pancreas, 685 

of pericardium, 498 

of peritoneum, 691 

of pharynx, 602 

of pia-arachnoid, 874, 929 

of pleura, 585 

of retina, 978 

of skin, 994 

of spinal cord, 937 

of spleen, 444 

of stomach, 613 

of testicles, 818 

of uterus, 775 

of uveal tract, 975 

of vagina, 806 

of vulva, 808 

passive, 59 
of lungs, 538 

venous, 59 
Hyperglucemia, 48 
Hyperidrosis, 1007 
Hyperinosis of plasma, 424 
Hyperkeratosis, 998 
Hypernephroma of kidney, 742 

of suprarenal bodies, 711 
Hyperplasia of mucous membrane 
uterus, 783 

of placenta, 812 
Hyperplastic perihepatitis, 696 
Hypersusceptibility, 270 
Hyperthyroidism, 703, 707 
Hypertrichosis, 1008 
Hypertrophic gastritis, 616 
Hypertrophy, 157 

definition of, 157 

etiology of, 157 

of bone-marrow, 464 

of bones, 841 

of brain, 889 

of cervix uteri, 783 

of heart, 494 

of kidneys, 737 

of liver, 670 

of lungs, 543 

of lymph-glands, 452 

of mammary glands, 830 

of muscles, 863 

of pericardium, 503 

of pituitary body, 713 

of prostate, 825 

of skin, 991 

of testicles, 817 

of tonsils, 605 

of uterus, 783 

pathological anatomy of, 158 
physiology of, 158 
Hypinosis of plasma, 424 



INDEX 



1025 



Hypophysis cerebri, 712. See also 

Pituitary body. 
Hypoplasia, definition of, 75 

of bones, 847 

of brain, 889 

of cerebellum, 889 

of cerebral hemispheres, 889 

of heart, 492 

of pericardium, 503 

of testicles, 816 
Hypopyon, 970 
Hypospadias, 814 
Hypostatic congestion, 56, 59 

pneumonia, 554, 557 



Ichthyosis, 992 

Icterus, 683. See also Jaundice. 
Idiosyncrasy in disease, 20 
Ileum, inflammation of, 635 
Immune bodies, chemistry of, 272 
Immunity, 19 

acquired bacterial, 255 

toxin, 256, 260 
active acquired, 256 
alexin theory of, 256 
antibacterial, 269 
antitoxic, 268 
bacterial, 265 

agglutination theory of, 259 
as applied to bacteriolysis, 266 

to cytolysis, 266 
natural, 255 
bacteriolytic theory of, 257 
definition of, 255 

Ehrlich's side-chain theory of, 263 

ferment theory of, 259 

natural toxin, 255, 259 

opsonin theory of, 258 

passive acquired, 256 

phagocytosis theory of, 257 

theories of, 256 

varieties of, 255 
Impetigo, 996 
Inanition, 39 
Indicanuria, 760 
Indigestion, 616 
Indigo in urine, 766 
Indirect transmission of disease, 409 
Indolent ulcer, 134 
Indurative pancreatitis, chronic, 688 
Infantilism 76 
Infarction, 66 
Infarcts, formation of, 66 

hemorrhagic, of lungs, 541 

pulmonary, 67 

subsequent changes in, 67 
Infection, 251, 253 

Friedberger's anaphylatoxin theory of, 
271 

paracolon, 294 
paratyphoid, 294 
Infectious disease, 37 

emphysema, definition of, 312 
etiology of, 312 
pathological anatomy of, 313 
65 



Infectious granulomata, 141 

theory of carcinoma 220 
Infestation, 251 
Infiltration, amyloid, 91 

dropsical, 95 

fatty, 80 

glycogenic, 94 

so-called, 78 
Inflammation, 117 

catarrhal, 135 

changes in blood-vessels in, 120 
chemical processes involved in, 125 
chronic, 137 

Cohnheim's emigration theory of, 118 
definition of, 117 
degenerative, 137 

changes in tissues in, 129 
diapedesis of red corpuscles in, 123 
diphtheritic, 131 
edema in, 125 
edematous, 130 
etiology, 130 
exudation in, 121 

of liquids in, 125 
fibrinous, 131 
fibroblastic cells in, 127 
Galen's definition, 118 
gangrenous, 137 
giant-cells in, 125 
granulation tissue in, 128 
hemorrhagic, 135 
historical note on, 118 
influence of nervous system in, 121 
large mononuclear phagocytic cells in, 

124 
necrotic, 137 

of arteries, 505. See also Arteritis. 
of biliary ducts, 678. See also Cholan- 
gitis. 

of bladder, 753. See also Cystitis. 

of bone-marrow, 465. See also Osteo- 
myelitis. 

of bones, 842. See also Ostitis. 

of brain substance, 910. See also 
Encephalitis. 

of bronchi, 532. See also Bronchitis. 

of bursa;, 862 

of cecum, 636 

of choroid, 977 
plexus, 922 

of ciliary body, 976 

of conjunctiva, 966. See also Con- 
junctivitis. 
of corium, 1001 

of cornea, 970. See also Keratitis. 

of dura mater, 870. See also Pachy- 
meningitis. 

of endocardium, 473. See also Endo- 
carditis. 

of epididymis, 818 

of esophagus, 610. See also Esophagi- 
tis. 

of Eustachian tube, 989 
of external ear, 985 
of eyelids, 903 
of Fallopian tubes, 799 



-1026 



INDEX 



Inflammation of gall-bladder, 680 
of hair-follicles, 1000 
of heart-muscle, 486. See also Myo- 
carditis. 
of ileum, 635 
of internal ear, 989 
of intestines, 633. See also Enteritis. 
of iris, 975 

of joints, 856. See also Arthritis. 

of kidney, 720. See also Nephritis. 
pelvis, 749 

of liver, 662. See also Hepatitis. 

of lungs, 548. See also Pneumonia. 

of lymphatic vessels, 521 

of lymph-glands, 454. See also Lymph- 
adenitis. 

of mammary glands, 829. See also 
Mastitis. 

of middle ear, 987. See Otitis media. 

of mouth, 594. See also Stomatitis. 

of muscles, 864. See also Myositis. 

of nails, 1008 

of nasal cavities, 525 

of nerves, 960. See also Neuritis. 

of nipples, 830 

of ovaries, 791 

of pancreas, 687. See also Pancreatitis. 
of pericardium, 498. See also Peri- 
carditis. 

of peritoneum, 693. See also Peritoni- 
tis. 

of pharynx, 602. See also Pharyngitis. 
of pia-arachnoid, 874, 930. See also 

Leptomeningitis. 
of pituitary body, 713 
of placenta, 811 

of pleura, 586. See also Pleuritis. 
of prostate, 824. See also Prostatitis. 
of pulp of teeth, 601 
of rectum, 639 
of retina, 979 

of salivary glands, 608. See also 

Parotitis. 
of sebaceous glands, 1000 
of skin, 994 

of spinal cord, 938. See also Myelitis. 

of spleen, 445. See also Splenitis. 

of stomach mucosa, 615. See also 

Gastritis. 
of subcutis, 1001 
of suprarenal bodies, 711 
of testicles, 818. See also Orchitis. 
of thymus gland, 712 
of thyroid gland, 700 
of tongue, 594. See also Glossitis. 
of trachea, 531 
of tunica vaginalis, 818 
of ureter, 750 
of uterus, 777 

of vagina, 806. See also Vaginitis. 

of vas deferens, 820 

of veins, 518. See also Phlebitis. 

of vitreous humor, 974 

of vulva, 808 

parenchymatous, 136 

pathological physiology of, 139 



Inflammation, phagocytosis in, 123 

phenomena of, in avascular tissues, 119 
in vascular tissues, 118 

phlegmonous, 134 

productive, 137 

proliferative changes in, 127 

in parenchymatous cells, 129 

pseudomembranous, 131, 287 

resolution after, 140 

role and fate of leukocytes in, 123 

round-cell infiltration in, 127 

secondary cellular degenerations in, 129 

serous, 130 

special forms of, 130 

specific, 141 

suppurative, 132 

types of, 130 

vascular theories of, 118 

Virchow's theory of, 118 
Influenza, definition of, 298 

etiology of, 298 

pathological anatomy of, 298 
Infusoria, 379 
Inheritance, blended, 23 

collateral, 21 

cumulative, 23 

diathetic, 23 

direct, 21 

familial, 23 

in etiology of disease, 21 

indirect, 21 

particulate, 23 

racial, 23 

reversionary, 23 
Insect transmission of disease, 409 

with cycle of development in in- 
termediate host, 410 

venom, poisoning from, 34 
Interstitial gastritis, 616 

pregnancy, 803 
Intestinal obstruction, 629 

sand, 653 
Intestines, abnormalities of, 626 

actinomycosis of, 648 

amyloid infiltration of mucosa of, 631 

anthrax of, 648 

atrophy of mucosa of, 631 

carcinoma of, 649 

congenital abnormalities in position of, 
627 

enlargement of, 626 
dilatation of, 627 
distortion of, 626 
edema of mucosa of, 632 
enterocystoma of, 627 
enteromycosis of, 648 
foreign bodies in, 653 
hemorrhage of, 631 
hernia of, 627 

hyperemia of, 631 > 
inflammation of, 633. See also Enteri- 
tis. 

internal strangulation of, 629 
intussusception of, 629 
invagination of, 629 
narrowing of, 626 



INDEX 



1027 



Intestines, parasites of, 651 

pigmentation of mucosa of, 631 

rupture of, 652 

sarcoma of, 648 

stenosis of, 627 

syphilis of, 647 

total absence of, 626 

tuberculosis of, 646 

tumors of, 648 

volvulus of, 629 
Intoxication, 253 

Intracardiac ganglia, degeneration of, 485 
Intussusception of intestine, 629 
Invagination of intestines, 629 
Inversion of uterus, 773 
Inverting ferments, 248 
Iodophilia, 423 
Iridocyclitis, 976 
Iris, 965, 974 
atrophy of, 974 

congenital abnormalities of, 974 

cysts of, 976 

syphilis of, 975 

tuberculosis of, 975 
Iritis, 975 
Irritation cells, 416 

Islands of Langerhans, diseases of, 686 



Jaundice, 683 

catarrhal, 635, 684 

etiology of, 683 

hematogenous, 684 

pathological anatomy of, 684 
Joints, ankylosis of, 855 

diseases of, 855 

distortions of, 855 

dropsy of, 856 

hemorrhage into, 856 

hyperemia of, 856 

luxation of, 855 

syphilis of, 861 

tuberculosis of, 860 
etiology of, 861 
pathological anatomy of, 861 
secondary disorders, 861 

tumors of, 862 



Kala-azar, 370 
Karyokinesis, 150 

altered, in necrotic cells, 115 
Karyokinetic figures, 421 
Karyolysis in cellular necrosis, 114 
Karyomitosis, 150 

Karyorrhexis in cellular necrosis, 114 
Keloid, 1005 
Keratitis, 970 

bullous, 971 

interstitial, 970 

phlyctenular, 971 

suppurative, 972 

ulcerative, 971 
Keratomalacia, 972 
Kidney, adenoma of, 744 

amyloid infiltration of, 739 



Kidney, anemia of, 718 
animal parasites of, 747 
atrophy of, 737 
bacteria in, 747 
calcification of, 739 
calculi in pelvis of, 749 
carcinoma of, 744 
cloudy swelling of, 737 
congenital anomalies of, 717 
cysts of, 745 
edema of, 719 

embolism of arteries of, 719 

fatty contracting, 726 
degeneration of, 738 
infiltration of, 738 

fibroma of, 741 

glycogenic infiltration of, 739 
• hemorrhage of, 719 

hyperemia of, 718 

hypernephroma of, 742 

hypertrophy of, 737 

inflammation of, 720. See also Nephri- 
tis. 

large white, 726 
lipoma of, 741 
malposition of, 717 
parasites of, 751 

parenchymatous degeneration of, 737 

pelvis, inflammation of, 749 

red granular, 730 

sarcoma of, 743 

secondary tumors of, 745 

syphilis, 741 

thrombosis of veins of, 719 

tuberculosis of, 741, 750 

tumors of, 751 
Knock-knee, 855 
Kobelt's tubes, cysts of, 797 
Kraurosis vulvae, 806 



Labile, elephantiasis of, 807 
Lachrymal organs, 970 
Lactosuria, 759 
Laennec's cirrhosis, 665 
Lamblia intestinalis, 368 
Landry's ascending paralysis, 943 
Langerhans, diseases of islands of, 686 
Langhans' giant-cell, 142 
Lardacein, 91 
Lardaceous disease, 91 
Laryngitis, catarrhal, acute, 527 
chronic, 527 

croupous, 528 

diphtheritic, 528 

edematous, 528 
Larynx, anatomical considerations of, 526 

anemia of, 527 

atrophy of, 529 

carcinoma of, 530 

congenital abnormalities of, 526 

edema of, 527 

fibroma of, 530 

glanders of, 529 

hemorrhages of, 527 

hyperemia of, 527 



1028 



INDEX 



Larynx, inflammation of, 527. See also 
Laryngitis. 

lepra of, 529 

papilloma of, 529 

parasites of, 530 

stenosis of, 529 

syphilis of, 529 

tuberculosis of, 528 
Lead, action of, 33 
Leather-bottle stomach, 616 
Leiomyoma, appearance of, 209 

definition of, 209 

etiology of, 209 

nature of, 211 

of uterus, 784 

seats of, 210 

structure of, 210 
Leishmania donovani, 371 
Leishmaniosis, 370 
Lens of eye, 964 
Leontiasis leprosa, 328 

ossium, 845 
Lepra of bones, 853 

of larynx, 529 

of testicles, 822 
Leprosy, 147 

definition of, 326 

etiology of, 326 

of cornea, 972 

of liver, 672 

of nerves, 963 

of skin, 1003 

pathological anatomy of, 327, 328 
Leptomeningitis, 874 
acute, 930 
chronic, 878, 930 

purulent myelitis secondary to, 939 
Leptothrix buccalis, 324 
Lesser omental cavity, cystic accumula- 
tions in, 690 
Leucin in urine, 766 
Leukemia, acute, 441 

blood in, 440 

bone-marrow in, 464 

definition of, 438 

etiology of, 438 

lymphatic type of, 440 

myeloid type of, 440 

of lymphatic glands, 460 

of spleen, 449 

pathological anatomy of, 438 

stomatitis, 600 
Leukoblasts, 416 
Leukocytes, 414 

granules of, 417 

large mononuclear, 415 

number of, 418 

pathological changes in, 422 

polymorphonuclear, 415 

polynuclear, 415 

proportions of different forms of, 418 
role and fate of, in inflammation, 123 
transitional, 415 
Leukocytosis, 428 
cachectic, 429 
character of blood in, 429 



Leukocytosis, etiology of, 428 
from hemorrhage, 429 
from malignant tumors, 429 
infectious, 428 
inflammatory, 428 

mechanical and thermal causes of, 429 

medicinal, 429 

pathogenesis of, 429 

pathological physiology of, 430 
Leukopenia, 431 
Leukoplakia, 595 
Leukoprotease, 126 
Leukorrhea, 806 
Levulosuria, 759 
Leydenia gemmipara, 366 
Lichen, 999 

Linguatula rhinaria, 406 
Linitis gastrica, 616 
Lipaciduria, 761 
Lipemia, 425 

Lipoid metamorphoses, 85 
Lipoma, appearance of, 174 

definition of, 174 

etiology of, 174 

nature of, 175 

of bones, 853 

of Fallopian tubes, 802 

of kidneys, 741 

of mammary glands, 832 

of pancreas, 698 

of pia-arachnoid, 882 

of skin, 1005 

of vulva, 809 

seats of, 175 

structure of, 175 
Lipomatosis of mammary glands, 831 
Lipuria, 763 

Liquefaction necrosis, 109 
definition of, 109 
pathological anatomy of, 109 
Liquor puris, 133 
Lithopedia, 97, 804 
Liver, abscess of, 662 

acquired changes of form of, 653 
of position of, 654 

actinomycosis of, 672 

adenoma of, 674 

amyloid infiltration of, 661 

anatomical considerations of, 653 

anemia of, 654 

atrophy of, 657 

carcinoma of, 675 

cirrhosis of, 663 

congenital changes of position of, 653 

malformations of, 653 
cyanotic induration of, 655 
cysts of, 677 

dropsical infiltration of, 661 
fatty degeneration of, 659 

infiltration of, 658 
gin-drinkers', 665 
hob-nail, 665 
hyperemia of, 654 
hypertrophy of, 670 
leprosy of, 672 
lymphadenoma of, 674 



INDEX 



1029 



Liver, parasites of, 677 

parenchymatous degeneration of, 659 

pigmentation of, 657 

red atrophy of, 655 

rupture of, 671 

sarcoma of, 674 

secondary carcinoma of, 676 

spots, 993 

syphilis of, 671 

tuberculosis of, 671 
Livores mortis, 116 
Local pigmentation, 102 
Locomotor ataxia, 944 
Ludwig's angina, 608 
Lungs, abscess of, 564 

actinomycosis of, 580 

active hyperemia of, 538 

anatomical considerations of, 537 

anemia of, 538 

atrophy of, 543 

carcinoma of, 581 

cavity formation in, 572 

congenital defects of, 538 

congestion of, 538 

cysts of, 584 

edema of, 540 

embolism of, 542 

emphysema of, 543 

gangrene of, 565 

glanders of, 579 

hemorrhage of, 540 

hemorrhagic infarcts of, 541 

hypertrophy of, 543 

inflammation of, 548 

parasites of, 584 

passive hyperemia of, 538 

sarcoma of, 580 

syphilis of, 578 

tuberculosis of, 566 

tumors of, 580 
Lupus, 1002 

erythematosus, 999 

verrucosa, 1003 

vulgaris, 321, 1003 
Luxation of joints, 855 
Lymphadenia ossea, 853 
Lymphadenitis, acute, 454 

chronic, 455 

suppurative, 455 
Lymphadenoma, appearance of, 185 

definition of, 184 

etiology of, 184 

nature of, 187 

of liver, 674 

of lymphatic glands, 461 
seats of, 185 
structure of, 186 
Lymphangiectasia, acquired, 522 

congenital, 522 
Lymphangioma, 181 

of brain, 921 
Lymphangitis, 521 
Lymphatic glands, 450 

anatomical considerations of, 450 
carcinoma of, 462 
endothelioma of, 462 



Lymphatic glands, functions of, 451 
Hodgkin's disease of, 461 
leukemia of, 460 
lymphadenoma of, 461 
lymphoma of, 461 
lymphosarcoma of, 462 
sarcoma of, 462 
syphilis of, 459 
tuberculosis of, 456 

individual groups of, 458 
tumors of, 461 
tissues, diseases of, 443 
vessels, anatomical considerations of, 
521 

dilatation of, 521 
inflammation of, 521 
parasites of, 523 
syphilis of, 522 
tuberculosis of, 522 
tumors of, 522 
Lymph-glands, amyloid infiltration of, 
453 

atrophy of, 452 

calcification of, 453 

fatty infiltration of, 453 

hyaline degeneration of, 453 

inflammation of, 454 

necrosis of, 453 

pigmentation of, 454 
Lymphocytes, 414 
Lymphogenic tuberculosis, 577 
Lymphoma of lymphatic glands, 461 
Lymphoprotease, 126 
Lymphosarcoma, 194 

of lymphatic glands, 462 
Lyssophobia, 357 



Macrocephaly, 888 
Macrocheilia, 522, 594 
Macroglossia, 522, 594 
Macules, 995 
Malaria, parasites of, 372 
pathological anatomy of, 376 

physiology of, 376 
role of mosquitoes in, 375 
Malignant edema, definition of, 311 
etiology of, 311 
pathological anatomy of, 312 
physiology of, 312 
papilloma of mammary glands, 835 
pustule, 1001 
Mallein, 305 

Malta fever, definition of, 303 
etiology of, 303 
pathological anatomy of, 303 

physiology of, 303 
synonyms of, 303 
Mammary glands, abnormal development 
in male, 829 
functional activity of, 829 
adenocarcinoma of, 835 
adenoma of, 833 
atrophy of, 830 
carcinoma of, 833 
medullary, 834 



1030 



INDEX 



Mammary glands, carcinoma of, simple, 

835 

squamous, 834 
chondroma of, 832 
cystadenoma of, 833 
cystosarcoma of, 833 
cysts of, 835 

early development of, 829 

fatty infiltration of, 831 

fibro-adenoma of, 831 

fibroma of, 831 

intracanalicular, 832 

hemorrhage from, 829 

hyperemia of, 829 

hypertrophy of, 830 

lipoma of, 832 

lipomatosis of, 831 

malignant papilloma of, 835 

myxoma of, 832 

myxomatous cancer of, 835 
degeneration of, 831 

osteoma of, 832 

Paget 's disease of, 834 

pathological anatomy of, 830 

results of cancer of, 835 

sarcoma of, 833 

scirrhous cancer of, 834 

supernumerary, 828 

syphilis of, 831 

tuberculosis of, 831 
Marantic thrombi, 68 
Mast-cell granules, 417 
Mastigophora, 366 
Mastitis, acute, 829 

chronic, 830 
Maximow, polyblast of, 152 
Measles, 352 

Meckel's diverticulum, 626 
Medullary canal, 882 

folds, 882 
Megakaryocytes, 417 
Megaloblasts, 421 
Meiostagmin reaction, 272 
Melanemia, 426 
Melanosarcoma, 197 
Melanosis, 974 
Melanuria, 761 
Melena neonatorum, 614. 
Membrane, pyogenic, 134 
Mendel's law, 23 

Meningitis, epidemic cerebrospinal, 877 

other organisms in, 278 

tuberculous, 878 
Meningocele, 873, 888 
Meningococcus, distribution of, 278 

pathogenesis of, 278 

pathological physiology of, 278 
Menorrhagia, 63, 776 
Menstruation, 775 
Mercury, action of, 33 
Mesarteritis, 505 
Mesencephalon, 883 
Mesenteric arteries, embolism of, 632 

thrombosis of, 632 
Metabolic pigmentation, 104 
Metabolism, disorders of, 39 



Metabolism in diabetes, 51 

of fat, 40 
Metaplasia, 155 
Metastasis, 65, 167 

pigment, 102 
Metencephalon, 883 
Methemoglobin in urine, 766 
Metritis, 777 

acute, 780 

chronic, 780 
Metrorrhagia, 63, 776 
Miasmatic disease, 38 
Microblasts, 421 
Microcephaly, 889 
Micrococcus catarrhalis, 284 

gonorrhoeae, 278 

melitensis, 303 

tetragenus, 284 
Micromyelia, 933 

Micro-organisms, entrance into body, 38 
Microphthalmia, 965 
Miliary tubercles, 319 

tuberculosis, 320 
Milium, 1007 
Mithridatization, 30 
Moles, hydatid, 813 
Molluscum contagiosum, 379, 1005 

appearances of, 380 

definition of, 379 

etiology of, 379 

seats of, 380 

structure of, 380 
Mononuclear leukocytes, large, 415 
Monsters, 239 

Morbid anatomy, definition of, 17 

physiology, definition of, 17 
Morgagni, hydatids of, 802 
Mosquitoes, role of, in malaria, 375 

in yellow fever, 351 
Mother wreath, 150 
Mouth, actinomycosis of, 600 

anemia of, 594 

hemorrhages of, 594 

syphilis of, 599 

tuberculosis of, 599 

tumors of, 600 
Mucoid degeneration, definition of, 88 
etiology of, 88 

microscopical appearances of, 89 

of bone-marrow, 464 

pathological anatomy of, 89 
physiology of, 90 

seats of, 89 
Mucopurulent cystitis, 754 
Mucous colitis, 639 
Mulberry calculi, 756 
Mummification, 112 
Mumps, 354 
Muscarin, 37 

Muscle tissue, regeneration of, 154 
Muscles, actinomycosis of, 869 

amyloid degeneration of, 868 

anemia of, 863 

anthrax of, 869 

atrophy of, 866 

calcification of, 868 



INDEX 



1031 



Muscles, coagulation necrosis of, 868 
embolism of arteries of, 863 
fatty degeneration of, 867 

infiltration of, 868 
glanders of, 869 
hematoma of, 868 
hemorrhage in, 863 
hyaline degeneration of, 868 
hyperemia of, 863 
hypertrophy of, 863 
parasites of, 869 

parenchymatous degeneration of, 867, 
868 

syphilis of, 869 

thrombosis of veins of, 863 

tuberculosis of, 869 

tumors of, 869 
Mutation, 23 
Mycetoma, 346 
Mycobacterium influenza?, 298 
organisms resembling, 299 

lepra;, 326 

tuberculosis, 313. See also Bacillus 

tuberculosis. 
Mycoses of skin, 1004 
Mycosis fungoides, 149, 199 

appearance of, 199 

associated conditions, 200 

etiology of, 199 

nature of, 200 

of external ear, 986 

structure of, 200 
Mydalein, 37 
Mydatoxin, 37 

Myelitis, hematogenous purulent, 939 
pressure-, 940 

secondary to purulent leptomeningitis, 
939 

transverse, secondary to injury or in- 
fectious disease, 939 
Myelocytes, 416 
Myeloid sarcoma, 195 
Myeloma, multiple, 188 

of bone-marrow, 466 

of bones, 854 
Myelomeningocele, 934 
Myeloplaxes, 417 
Myiasis, 406 
Myocarditis, acute, 487 
circumscribed, 487 
diffuse, 488 

chronic, 489 
Myocardium, 481. See also Heart- 
muscle. 
Myofibroma of uterus, 784 

of vagina, 807 

of vulva, 809 
Myoma of bladder, 758 

of mammary glands, 832 
Myopathic muscular atrophy, 867 
Myositis, chronic, 865 
productive, 865 
suppurative, 865 

disseminated acute, 864 

hemorrhagic, 864 

localized acute, 864 



Myositis ossificans progressiva, 865 

ossifying, 865 

serous, 864 

suppurative, 864 
Myotonia congenita, 867 
Myxedema, 706 
Myxoma, appearance of, 173 

definition of, 173 

etiology of, 173 

nature of, 174 

of bladder, 758 

of bones, 853 

of mammary glands, 832 

of testicles, 822 

seats of, 173 

structure of, 173 
Myxomatous degeneration of mammary 
glands, 831 
of testicles, 817 



Nails, 1008 

inflammation of, 1008 

tumors of, 1008. 
Nasal cavities, anatomical considerations 
of, 524 

congenital abnormalities of, 524 

edema of, 524 

foreign bodies in, 526 

hemorrhage of, 524 

hyperemia of, 524 

inflammation of, 525 

parasites of, 526 

syphilis of, 525 

tuberculosis of, 525 

tumors of, 526 
Necator americanus, 399 
Necrobiosis, 105 
Necroses, focal, 112 
Necrosis, 105 

circulatory derangements in, 106 

coagulation, 107 

definition of, 105 

etiology of, 105 

intoxications in, 106 

mechanical agents in, 106 

of bone-marrow, 464 

of bones, 846 

of lymph-glands, 453 

of pancreas, 686 

of skin, 993 

pressure-, of pharynx, 606 
trophic derangements in, 106 
Necrotic cells, altered karyokinesis in, 115 

inflammation, 137 
Nematodes, 395 
Nephritis, acute catarrhal, 722 
diffuse, 723 
hemorrhagic, 724 
parenchymatous, 722 
arteriosclerotic, 730, 736 
cardiac changes in, 736 
chronic, 726 

hemorrhagic, 726 
interstitial, 729 
primary, 730 



1032 



INDEX 



Nephritis, chronic interstitial, secondary, 
729 

parenchymatous, 726 
desquamative, 722 
edema in, 736 
embolic suppurative, 724 
etiology of, 720 
gouty, 730 

non-suppurative acute interstitial, 724 

pathological anatomy of, 721 
physiology of, 732 

secondary interstitial, 726 

senile, 737 

suppurative, 725 

tube-casts in, 733 

uremia in, 736 

urine in, 733, 735 
Nerve tissues, tumors from, 204 
Nerve-cells, 892 

functions of, 896 
Nerve-fibers, 897 

functions of, 897 
Nerve-poisons, poisoning from, 36 
Nerves, 958 

atrophy of, 959 

degeneration of, 959 

edema of, 958 

hemorrhage of, 958 

leprosy of, 963 

syphilis of, 963 
Nervous system, central, concussion of, 
917 

injuries to, 917 
general pathological anatomy of, 891 
influence of, in inflammation, 121 
sympathetic, 883 
tissue, regeneration of, 154 
Neurin, 37 
Neuritis, 960 

interstitial, acute, 961 

chronic, 962 
parenchymatous, 962 
Neuroblasts, 882 
Neuro-epithelioma, 207 

of brain, 920 
Neuroglia, degeneration of, 898 
Neuroglioma, ganglionar, of brain, 920 
Neuroma, appearance of, 208 
definition of, 208 
etiology of, 208 
nature of, 209 
of suprarenal bodies, 711 
seats of, 208 
structure of, 209 
Neuron, 885 

Neuropathic muscular atrophy, 866 

secondary, 867 
Neutrophiles, 415 
Neutrophilic granules, 418 
Nevus, 991 

New growths, autonomous, 159 
Nigrities, 598 
Nitrifying ferments, 248 
Noma, 597 

Non-contagious disease, 37 
Normoblasts, 421 



Nucleo-albuminuria, 762 
Nutmeg-liver, 655 
Nutrition, disorders of, 39 
in disease, 20 



Obesitas cordis, 482 
Obesity, associated conditions, 41 
causes of, 40 

pathological anatomy of, 41 
Ochronosis, 760 
Odontomata of teeth, 602 
Oidiomycosis, 348 
O'idium albicans, 347 
Oligemia, 424 
Onychia, 1008 
Onychogryphosis, 1008 
Oochronosis, 105 
Oophoritis, 791 

chronic, 792 
Ophthalmitis, sympathetic, 980 
Opisthorchis felineus, 382 

sinensis, 382 
Opsonin theory of immunity, 258 
Optic nerve, atrophy of, 982 
inflammation of, 981 
syphilis of, 982 
tuberculosis of, 982 
tumors of, 982 

thalami, 883 
Orbit, 983 

tumors of, 983 
Orchitis, acute, 878 

chronic, 819 
Ossification, 98 
Osteatosis, 1007 
Osteo-arthritis, 859 
Osteo-arthropathy, hypertrophic, 843 
Osteoclasts, 845 
Osteogenesis imperfecta, 837 
Osteoma, appearance of, 179 

definition of, 179 

etiology of, 179 

nature of, 180, 181 

of bones, 853 

of brain, 922 

of mammary glands, 832 

of testicles, 822 

seats of, 180 
Osteomalacia, conditions associated with, 
849 

definition of, 848 

etiology of, 848 

pathological anatomy of, 848 
Osteomyelitis, 465 

conditions associated with, 844 

definition of, 843 

etiology of, 843 

pathological anatomy of, 844 
Osteoporosis, inflammatory, 845 
Osteopsathyrosis, 848 
Osteosarcoma, 195 

true, 196 
Osteosclerosis, 845 
Ostitis, 843 

chronic, 844 



INDEX 



1033 



Ostitis, chronic, etiology of, 844 
pathological anatomy of, 845 

condensing, 845 

deformans, 846 
Otitis media, 987 
catarrhal, 988 
purulent, 988 
Ovaries, anatomical considerations of, 790 

carcinoma of, 796 

changes in position of, 790 

congenital abnormalities of, 790 

connective-tissue tumors of, 792 

cystomata of, 793 

dermoid cysts of, 795 

development of, 790 

follicular cysts of, 793 

hemorrhage from, 791 

hyperemia of, 791 

sarcoma of, 792 

tuberculosis of, 792 
Overfeeding, 40 
Oxalate of lime in urine, 764 
Oxaluria, 52 
Oxidizing ferments, 248 
Oxyphile granules, 417 
Oxyuris vermicularis, 396 
Ozena, 525 



Pacchionian bodies, 880 
Pachydermia laryngis, 528 
Pachymeningitis adhesiva, 930 < 

cervicalis, 928 

external tuberculous, 928 

internal hemorrhagic, 870 

productive, 872 

suppurative external, 871 
Paget' s disease of mammary glands, 834 
Pancreas, amyloid infiltration of, 686 

atrophy of, 685 

carcinoma of, 689, 698 

cirrhosis of, 688 

congenital abnormalities of, 685 
cysts of, 689 
fat-necrosis of, 686 
fibroma of, 698 
hemorrhage of, 685 
hyperemia of, 685 

inflammation of, 687. See also Pan- 
creatitis. 
lipoma of, 698 
necrosis of, 686 
parasites of, 698 

parenchymatous degeneration of, 685 
pigmentation of, 686 
sarcoma of, 689, 698 
syphilis of, 689 
tuberculosis of, 689 
Pancreatic acne, 690 
calculi, 690 

disease, pathological physiology of, 688 

duct, obstruction of, 690 
Pancreatitis, acute hemorrhagic, 687 
suppurative, 687 

chronic indurative, 688 
Pandemic disease, 38 



Pannus, 968 
Papillitis, 981 
Papillo-edema, 981 
Papilloma, appearance of, 212 

definition of, 212 

etiology of, 212 

nature of, 215 

of bladder, 757 

of larynx, 529 

of penis, 815 

of vagina, 807 

seats of, 213 

structure of, 214 
Papillomatous tumors of vulva, 809 
Papules, 995 
Paracolon infection, 294 
Paragonimus westermanii, 383 
Parakeratosis, 998 
Paralbumin, 793 

Paralysis, general progressive, 916 
, Landry's ascending, 943 
Paramecium coli, 379 
Parametritis, 777 
Parametrium, 803 
Paraphimosis, 814 
Parasites, animal, 38 

of blood, 442 

of bones, 854 

of bronchi, 537 

of intestines, 651 
animal, 652 

of kidneys, 751 

of larynx, 530 

of liver, 677 

of lungs, 584 

of lymphatic vessels, 523 

of malaria, 372 

of muscles, 869 

of nasal cavities, 526 

of pancreas, 698 

of pericardium, 502 

of pleura, 593 

of spleen, 450 

of thyroid gland, 705 

of uterus, 790 

vegetable, 37 
Parasitic diseases, 38 
Parathyroid glands, 707 
Paratyphoid fever, 646 

infection, 294 

intestinal lesions in, 295 
nature of, 295 

pathological anatomy of, 295 
Parenchymatous degeneration of heart, 
481 

of kidneys, 737 

of fiver, 659 

of muscles, 867 

of pancreas, 685 
goiter, 700 
hepatitis, 662 
inflammation, 136 
Paresis, 916 

Parinaud's conjunctivitis, 968 
Paronychia, 1008 
Paroophoron, 790 



1034 



INDEX 



Parostitis, 843 

Parotid gland, tumors of, 609 
Parovarium, 790 

cysts of, 796 
Pathological anatomy, definition of, 17 

chemistry, definition of, 17 

physiology, definition of, 17 
Pathology, definition of, 17 

general, 17 

special, 17 
Pearl disease, 143 
Pediculus vestamenti, 355 
Pellagra, 360 
Pemphigus, 996 
Penis, 814 

carcinoma of, 815 

chancroid of, 815 

concretions under prepuce of, 816 

condyloma acuminatum of, 815 

cysts of, 816 

epithelioma of, 815 

injuries of, 816 

papilloma of, 815 

secondary lesions of, 815 

syphilitic chancre of, 815 

tuberculosis of, 815 
Pentosuria, 52, 759 
Peptic ulcer, 134, 617 
Perforating ulcer, 134 
Perforation of esophagus, 611 
Periangiocholitis, 669 
Periappendiceal abscess, 638 
Peri-arteritis, 505 

nodosa, 507 
Peribronchitis, 534 
Pericarditis, 498 

acute, terminations of, 500 

conditions associated with, 502 

dry, 499 

fibrinous, 499 

hemorrhagic, 500 

purulent, 500 

serofibrinous, 500 
Pericardium, 498 

actinomycosis of, 502 

amyloid infiltration of, 504 

atrophy of, 504 

calcareous infiltration of, 504 

fatty degeneration of, 504 

hemorrhages of, 498 

hyaline degeneration of, 504 

hyperemia of, 498 

hypertrophy of, 503 

hypoplasia of, 503 

inflammation of, 498 

parasites in, 502 

syphilis of, 502 

tuberculosis of, 502 

tumors of, 502 
Perichondritis, 528, 595 
Perihepatitis, 670 

hyperplastic, 696 
Perimastitis, 830 
Perimetritis, 777 
Perinephric abscess, 725 
Periorchitis, 819 



Periorchitis prolifera, 820 
Periostitis, conditions associated with, 
843 

definition of, 842 
etiology of, 842 
ossifying, 843 

pathological anatomy of, 842 

purulent, 842 

results of, 843 

simple, 842 

syphilitic, 852 
Periphlebitis, 518 
Periprostatitis, 824 
Perisplenitis, 450 
Perithelioma, 200 

of brain, 921 
Peritoneum, congenital abnormalities of, 
691 

dropsy of, 692 
hemorrhage of, 691 
hyperemia of, 691 

inflammation of, 693. See also Peri- 
tonitis. 
tuberculosis of, 696 
Peritonitis, acute, effects of, 695 
general, 694 
localized, 694 
chronic, 695 
etiology of, 693 
Perityphlitis, 636 

Pernicious anemia, progressive, 435 
» blood in, 436 

etiology of, 435 
pathogenesis of, 435 
pathological anatomy of, 436 
Pes calcaneus, 855 
equinus, 855 
valgus, 855 
varus, 855 
Petechias, 62 

Pfeiffer's phenomenon, explanation of, 
267 

Phagedenic ulcer, 134 

ulceration of cervix, 780 
Phagocytic cells, large mononuclear, in 

inflammation, 124 
Phagocytosis in inflammation, 123 

theory of immunity, 257 
Pharyngitis, catarrhal, 602 
chronic, 603 

phlegmonous, 603 

pseudomembranous, 603 
Pharyngomycosis leptothricia, 324, 607 
Pharynx, 602 

anemia of, 602 

diphtheria of, 606 

edema of, 602 

hemorrhages of, 602 

hyperemia of, 602 

pressure necrosis of, 606 

syphilis of, 607 

tuberculosis of, 607 

tumors of, 608 
Phimosis, 814 
Phlebectasia, 519 
Phlebitis, acute, 518 



INDEX 



1035 



Phlebitis, chronic, 518 
Phleboliths, 72, 518 
Phlebosclerosis, 518 
Phlegmon, 1002 
Phlegmonous cystitis, 754 

inflammation, 134 

pharyngitis, 603 

stomatitis, 596 
Phosphates in urine, 764 
Phosphaturia, 53 
Phosphorus, action of, 32 

metabolism of, 52 
Photogenesis of bacteria, 251 
Phthisis, acute caseous, 569 

chronic ulcerative, 569 

fibroid, 569, 573 
Physiology, morbid, 17 

pathological, 17 
Physometra, 775 
Pia-arachnoid, 873, 929 

anemia of, 874 

calcareous infiltration of, 929 

cholesteatoma of, 881 

edema of, 874 

endothelioma of, 880 

hemorrhage of, 929 

hyperemia of, 874, 929 

lipoma of, 882 

sarcoma of, 881 

syphilis of, 879, 930 

teratoma of, 882 

tuberculosis of, 930 

tumors of, 880, 931 
Pigment metastasis, 102 
Pigmentary cirrhosis, 670 

infiltration of choroid plexus, 923 
Pigmentation, 99 

from the exterior, 99 

hematogenous, 101 

hepatogenous, 104 

metabolic, 104 

of bone-marrow, 464 

of liver, 657 

of lymph-glands, 454 

of mucosa of intestines, 631 

of pancreas, 686 

of spleen, 448 

of stomach, 620 

of suprarenal bodies, 709 
Pineal gland, 715, 883 
Pinguecula, 969 
Pink-eye, 968 
Pituitary body, 712 
adenoma of, 714 
amyloid infiltration of, 714 
circulatory disturbances of, 713 
colloid degeneration of, 714 
cysts of, 714 
hypertrophy of, 713 
infectious diseases of, 714 
inflammation of, 713 
pathological physiology of, 714 
sarcoma of, 714 
Pityriasis versicolor, 1004 
Placenta, 810 

hyperplasia of, 812 



Placenta prsevia, 810 

succenturiata, 810 

syphilis of, 812 

tuberculosis of, 812 
Placental infarcts, 811 

polypi, 813 
Placentitis, 811 
Plaques jaunes, 910 
Plasma cells, 416 

hyperinosis of, 424 

hypertonicity of, 424 

hypinosis of, 424 

of blood, 419 

pathological changes in, 423 
Plasmodia, parthenogenesis of, 374 

sporogony of, 374 
Plasmodium falciparum, 374 

malarise, 374 

vivax, 373 
Plethora, 424 

apocoptica, 424 

hydremica, 424 

vera, 424 
Pleura, 585 

anatomical considerations of, 585 

chronic thickening of, 590 

chylous effusion in, 586 

hyperemia of, 585 

inflammation of, 586. See also Pleu- 
ritis. 

parasites of, 593 

petechial hemorrhages of, 585 

syphilis of, 591 

tuberculosis of, 591 

tumors of, 592 
Pleurisy, 586. See also Pleuritis. 
Pleuritis, bread-and-butter, 588 

etiology of, 586 

fibrinous, 587 

hemorrhagic, 590 

lesions in other parts associated with, 
590 

pathological anatomy of, 587 
physiology of, 591 

purulent, 589 

serofibrinous, 589 

tuberculous, 591 
Pleurogenic purulent pneumonia, 564 
Plexiform angiosarcoma, 201 
Pneumaturia, 761 
Pneumonia alba, 563 

aspiration, 554, 557 

bronchogenic, complications in, 574 

cheesy, 558. See also Pneumonia, 
tuberculous. 

classification of, 548 

congenital syphilitic, 563 

croupous, 280, 549. See also Pneu- 
monia, fibrinous. 

deglutition, 554 

desiccans, 565 

fibrinous, 549, 550 
definition of, 549 
etiology of, 549 
lesions associated with, 552 
pathological anatomy of, 550 



1036 



INDEX 



Pneumonia, fibrinous, pathological physi- 
ology of, 552 
stage of congestion or engorgement 
in, 550 

of consolidation or hepatization in, 
550 

of resolution in, 551 
unusual characters of, 552 
terminations of, 553 
fibrous, 560 

classification of, 560 
peribronchial, 562 
perivascular, 562 
pleurogenic, 562 
secondary, 562 
hypostatic, 554, 557 
other forms of, 283 
organisms in, 284 
pathological physiology of, 282 
purulent, 563 

bronchogenic, 563 
hematogenic, 563 
pleurogenic, 564 
tuberculous, 558 
etiology of, 558 
lesions associated with, 560 
pathological anatomy of, 558 
white, 563 
Pneumonic tuberculosis, 569 
Pneumonokoniosis, 99, 560 
Pneumopericardium, 503 
Pneumothorax, 586 
Poikilocytosis, 420 
Poisons, classification of, 31 
corrosive, action of, 31 
definition of, 29 
effect of, 30 
elimination of, 31 
fate of, after ingestion, 30 
general action of, 29 
in disease, 20 
in etiology of disease, 29 
organic, action of, 32 
parenchyma, action of, 32 
Polio-encephalitis, 943 
Poliomyelitis, 361 
acute anterior, 941 
chronic anterior, 951 
superior, 943 
Polyblast of Maximow, 152 
Polychromatophitia, 422 
Polycoria, 974 
Polycythemia, 427 

with chronic cyanosis and enlarged 
spleen, 428 
Polymastia, 829 

Polymorphonuclear leukocytes, 415 
Polymyositis, 864 

secondary acute, 867 
Polyneuritis, 962 
Polynuclear leukocytes, 415 
Polyorchism, 816 
Polypi, 526, 811 

of uterus, 783 

placental, 813 
Polypoid tumors of urethra, 770 



Polyuria, 759 
Pons, anatomy of, 884 
Porencephaly, 890 
Porocephalus constrictus, 406 
Portal cirrhosis, changes associated with, 
667 

morbid anatomy of, 666 
pathological physiology of, 668 
vein, embolism of, 656 
thrombosis of, 656 
Posthitis, 814 
Postmortem lividity, 57 
Precipitin, 265 
Pregnancy, abdominal, 805 
extra-uterine, 803 
interstitial, 803 
tubal, 803 
Pressure, pathological effects of, 24 
Pressure-myelitis, 940 
Proctitis, 639 

Productive inflammation, 137 
Progressive muscular atrophy, 866 
Prolapse of rectum, 630 

of uterus, 773 
Proliferation cysts, 232 
Proptosis, 983 
Prosencephalon, 883 
Prostate, 824 

abscess of, 824 

amylaceous bodies of, 825 

atrophy of, 824 

carcinoma of, 828 

concretions of, 825 

cysts of, 828 

fatty degeneration of, 825 

hypertrophy of, 825 
results of, 827 

sarcoma of, 827 

tuberculosis of, 825 
Prostatitis, chronic, 824 

phlegmonous, 824 

simple, 824 

suppurative, 824 
Protein metabolism, disorders of, 44 
Proteins of bacteria, 247 
Proteolytic ferments, 248 
Proteus infection, 350 
Prothrombin, 69 
Protozoa, 364 
Prurigo, 999 

Psammoma, 97, 203, 204 

of brain, 922 
Pseudoarthroses, 841 
Pseudohermaphroditism, 814 
Pseudohydrophobia, 357 
Pseudohypertrophic muscular atrophy, 

867 

Pseudoleukemia, 441 

cutis, 200 

infantum, 441 
Pseudomembranous cystitis, 754 

enteritis, 634 

gastritis, 614 

inflammation, 131, 287 

pharyngitis, 603 

stomatitis, 596 



INDEX 



1037 



Pseudomembranous vaginitis, 806 

Pseudomucin, 793 

Pseudotrichinosis, 864 

Pseudotuberculosis, 324 

Psoas abscess, 869 

Psoriasis, 998 

Pterygium, 969 

Ptomains, poisoning from, 36 

Ptosis of eyelids, 983 

Puerperal infections, 780 

etiology of, 780 

pathological anatomy of, 780 
Pulmonary artery, stenosis and atresia of, 
469 

Pulp of teeth, inflammation of, 601 
Purin metabolism, disorders of, 45 
Purulent pneumonia, 563 
Pustules, 135, 995 
Putrefaction, 248 
Pyelitis, 749 
Pyelonephritis, 750 
suppurative, 725 
Pyemia, 253 

Pyknomorphous state, 893 
Pyogenic albumosuria, 761 

membrane, 134 
Pyometra, 775 
Pyonephrosis, 750 
Pyopericardium, 500 
Pyopneumothorax, 586 
Pyorrhea alveolaris, 596 
Pyosalpinx, 801 
Pyothorax, purulent, 589 



Quinsy, 605 



Rabies, 356 
from bites, 357 

microscopical anatomy of, 357 
pathological anatomy of, 357 
period of incubation in, 357 
preventive inoculation for, 357 
season for, 357 
virus of, 356 

Race in disease, 20 

Rachischisis, 933 

Ranula, 601 

Reaction, meiostagmin, 272 
Rectocele, 773 
vaginal, 805 
Rectum, inflammation of, 639 

prolapse of, 630 
Red atrophy of liver, 655 
corpuscles, 413 

ameboid movements of, 421 

basic degeneration of, 422 

nucleated, 421 

pathological changes in, 420 

pigmentation of, 422 

shape of, 420 

size of, 420 

skeined, 414 

vacuolation of, 422 
Regeneration, definition of, 149 



Regeneration, etiology of, 149 
of adipose tissue, 154 
of bone, 153 
of cartilage, 153 
of epithelium, 151 
of fibrous connective tissue, 151 
of glandular organs, 154 
of muscle tissue, 154 
of nervous tissue, 154 
of skin, 993 

pathological anatomy of, 150 
physiology of, 155 
Relapsing fever, definition of, 339 
etiology of, 339 
pathological anatomy of, 340 
physiology of, 340 
Renal sand, 749 
Repair of wounds, 137 
Reproductive organs, diseases of, 771 
Resolution after inflammation, 140 
Respiratory system, diseases of, 524 
Retention cysts, 232 
Retina, 965, 978 

anemia of, 978 

atrophy of, 978 

detachment of, 979 

glioma of, 206 

hemorrhage of, 978 

hyperemia of, 978 

pigmentary degeneration of, 979 

syphilis of, 980 

tuberculosis of, 980 

tumors of, 980 
Retinitis, albuminuric, 979 

chronic, 979 

diabetic, 979 

pigmentosa, 979 

purulent, 979 
Retroflexion of uterus, 773 
Retrograde change, 156 
Retrogressive processes, 76 
Retropharyngeal abscess, 603 
Retro-uterine hematocele, 776 
Retroversion of uterus, 773 
Rhabdomyoma, appearance of, 212 

definition of, 211 

etiology of, 211 

nature of, 212 

of testicles, 822 

seats of, 212 

structure of, 212 
Rhachischisis, 888 
Rheumatism, 358 
Rhinitis, chronic, 525 

diphtheritic, 525 
Rhinoliths, 526 
Rhinoscleroma, 148, 303 
Rhizopoda, 364 

Ribbert's theory of tumors, 160 

Ricin, poisoning from, 34 

Rickets, conditions associated with, 839 

congenital, 837 

definition of, 837 

etiology of, 837 

minute changes of, 838 

pathological anatomy of, 838 



1038 



INDEX 



Rigor mortis, 115 

Ring abscess of cornea, 972 

bodies, 421 
Ringworm, 1004 
Rocky mountain fever, 362 
Rodent ulcer, 1006 
Round ulcer, 617 

Round-cell infiltration in inflammation, 
127 

sarcoma, 193 
Round-worms, 395 
Rupture of intestines, 652 

of uterus, 775 
Russell's fuchsin bodies, 87 



Schistosomum haematobium, 382 

japonicum, 383 
Schizomycetes, 242 
Sclera, 964, 972 
injury to, 973 
Sclerema, 992 
Scleritis, 972 
Scleroderma, 992 
Sclerosis of brain, atrophic, 899 
diffuse, 899 
disseminated, 899, 915 
hypertrophic nodular, 900 
lobar, 914 
multiple, 915 
of spinal cord, combined, 951 
lateral, 952 

amyotrophic, 949 
posterior, 944 
Scrofula, 322, 458 
Scrotum, 814 

elephantiasis of, 815 
Scutula, 1004 
Sebaceous cysts, 1007 
glands, 1006 

inflammation of, 1000 
tumors of, 1007 
Seborrhea, 1007 

Secondary carcinoma of liver, 676 

Segmentation, indirect, 150 

Sella turcica, 712 

Seminal vesicles, 828 

Septicemia, 253 

Sequestrum of bone, 846 

Serofibrinous pleuritis, 589 

Serous inflammation, 130 

Serpent venom, poisoning from, 34 

Serpiginous ulcer, 134 

Sex in disease, 20 

Siderosis, 100, 562 

Sinus thrombosis of dura mater, 870 

Sinuses, 134 

Skin, actinomycosis of, 1003 
anatomy of, 990 
anemia of, 993 
atrophy of, 991 

benign cystic epithelioma of, 1006 

circulatory disturbances of, 993 

congenital abnormalities of, 991 

crusts of, 995 

edema of, 994 

fibroma of, 1005 

glanders of, 1003 

hemorrhage into, 994 

hyperemia of, 994 

hypertrophy of, 991 

lenticular carcinoma of, 1006 

lipoma of, 1005 

mycoses of, 1004 

necrosis of, 993 

pigment of, 990 

regeneration of, 993 

sarcoma of, 1006 

scales of, 995 

specific inflammations of, 1002 
squamous epithelioma of, 1006 
syphilis of, 1003 



Saccharomyces hominis, 348 
Saccharomycosis, 148, 348 
Saccular aneurysm, 514 
Salivary ducts, diseases of, 609 

glands, inflammation of, 608. See also 
Parotitis. 
Salpingitis, acute, 799 

diphtheritic, 800 

chronic, 801 
Sapremia, 253 
Sarcoma, alveolar, 194 

appearances of, 189 

definition of, 189 

etiology of, 189 

giant-celled, 195 

myeloid, 195 

nature of, 191 

of bones, 853 

of brain, 920 

of dura mater, 929 

of Fallopian tubes, 802 

of intestines, 648 

of kidney, 743 

of liver, 674 

of lungs, 580 

of lymphatic glands, 462 

of mammary glands, 832 

of ovaries, 792 

of pancreas, 689, 698 

of pia-arachnoid, 881 

of pituitary body, 714 

of prostate, 827 

of skin, 1006 

of spinal cord, 957 

of spleen, 449 

of suprarenal bodies, 711 

of testicles, 822 

of thyroid gland, 705 

of urethra, 770 

of uterus, 785 

of vagina, 807 

of vulva, 809 

round-celled, 193 

seats of, 190 

spindle-celled, 193 

structure of, 190 
Sarcosporidia, 378 
Scabies, 1004 
Scales, skin, 995 
Scarlet fever, 353 



INDEX 



1039 



Skin, tuberculosis of, 1002. See also 
Lupus. 
ulcers of, 1002 

variations in pigmentation of, 993 
xanthoma of, 1005 
Smegma bacillus, 324 
Soft chancre, definition of, 302 
etiology of, 302 
mixed infection in, 302 
pathological anatomy of, 302 
physiology of, 303 
Soil transmission of disease, 409 
Specific inflammations, 141 
Spermatocele, 823 
Spider cells, 885 
Spina bifida, 933 
Spinal cord, anatomy of, 931 
anemia of, 937 
carcinoma of, 957 
circulatory disturbances of, 936 
degenerations of, secondary, 953 

of white matter of, 952 
dilatation of central canal of, 933 
diseases of, 928 
double, 933 
hemorrhage of, 937 
heterotopia of gray matter of, 933 
hyaline degeneration of, 936 
hyperemia of, 937 
primary degenerations of, 943 
sarcoma of, 957 
sclerosis of, combined, 951 
lateral, 952 

amyotrophic, 949 
syphilis of, 943 
total absence of, 932 
tuberculosis of, 943 
unusual length of, 933 
varicose veins of, 937 
nerves, diseases of ganglia of, 958 
Spindle-celled sarcoma, 193 
Spirilla, diseases due to, 330 
Spirillacese, 242 
Spirillum, 243 
berolinense, 333 
cholerae asiatica?, 330 
Metschnikovii, 333 
of Finkler and Prior, 333 
tyrogenicum, 333 
vincenti, 340 
Spirochseta carteri, 339 
duttoni, 339 
novyi, 339 
obermeieri, 339 
pallida, 334 
pertenui, 341 
Spirochetes, diseases due to, 344 
Splanchnoptosis, 621 
Spleen, abnormal development of, 444 
abscess of, 446 
amyloid infiltration of, 448 
anatomic considerations of, 443 
anemia of, 444, 447 
atrophy of, 448 
calcification of, 449 
carcinoma of, 449 



Spleen, chronic inflammation of, 447 
circulatory disturbances of, 444 
cysts of, 449 

embolism of artery of, 445 

endothelioma of, 449 

enlarged, and chronic cyanosis, polycy- 
themia with, 428 

hemorrhage in, 445 

Hodgkin's disease of, 449 

hyaline degeneration of, 448 

hyperemia of, 444 

inflammation of, 445 

leukemia of, 449 

malposition of, 444 

movable, 444 

parasites of, 450 

pathological physiology of, 443 

pigmentation of, 448 

sarcoma of, 449 

syphilis of, 450 

thrombosis of vein of, 445 

tuberculosis of, 450 
Splenic stones, 445 
Splenitis, circumscribed, 446 

diffuse, 445 

terminations of, 446 
Splenomegaly, 447 
Spondylitis deformans, 859 
Spongioblasts, 882 
Sporothricosis, 149, 349 
Sporothrix beurmanii, 349 
Sporozoa in birds and cold-blooded ani- 
mals, 376 
Spring catarrh, 966 
Spurious aneurysm, 517 
Squamous epithelioma, 227 
Staphylococcus group, 273 

pyogenes albus, 275 
aureus, 273 

distribution of, 274 
pathogenicity of, 274 
pathological physiology of, 274 
citreus, 275 
Staphyloma, 970 
Starvation, 39 
Stasis of blood, 60 
Status lymphaticus, 452, 712 
Staubzellen, 560 
Stimulation cells, 416 
Stegomyia fasciata, 351 
Stenosis of bile-ducts, 680 

of bronchi, 534 

of esophagus, 610 

of Fallopian tubes, 798 

of intestines, 627 

of larynx, 529 

of uterus, 775 

of vagina, 805 
Stercoral typhlitis, 636 
Stomach, alterations in position of, 621 

amyloid infiltration of, 620 

anemia of, 613 

atrophy of glands of, 620 

calcification of, 620 

carcinoma of, 623 

congenital defects, 613 



1040 



INDEX 



Stomach, connective-tissue tumors of, 622 

dilatation of, 621 

epithelial tumors of, 622 

fatty degeneration of, 620 

hemorrhage of, 613 

hyperemia of, 613 

infectious diseases of, 622 

inflammation of mucosa of, 614 

leather-bottle, 616 

pigmentation of, 620 
Stomatitis, 594 

aphthous, 595 

catarrhal, 595 

conditions associated with, 598 

gangrenous, 597 

leukemic, 600 

parasitic, 598 

phlegmonous, 596 

pseudomembranous, 596 

ulcerative, 596 
Strangulated hernia, 629 
Strangulation of hernia, internal, 629 
Streptococcus, distribution of, 276 

intracellularis meningitidis, 277 

pathogenesis of, 276 

pathological physiology of, 276 

pyogenes seu erysipelatis, 275 
Streptothrix madurae, 346 
Stricture of urethra, 769 
Strongyloides intestinalis, 400 
Strongyloplasma hominis, 380 
Strongylus apri, 405 

subtilis, 405 
Struma, 700. See also Goiter. 

malignant, 705 
Strumitis, 704 
Stye, 983 

Subcutis, inflammation of, 1001 
Sudamina, 1008 
Suffocation, 28 
Suggillation, 63 
Sulphates in urine, 766 
Suppurative diseases, 273 

definition of, 273 

etiology of, 273 
inflammation, 132 
pancreatitis, acute, 687 
Suprarenal bodies, accessory, 709 

adenoma of, 711 

amyloid infiltration of, 709 

anatomical considerations of, 708 

congenital anomalies of, 709 

fatty degeneration of, 709 

ghoma of, 711 

hemorrhage of, 710 

hypernephroma of, 711 

inflammation of, 710 

neuroma of, 711 

pigmentation of, 709 

sarcoma of, 711 

syphilis of, 710 

tuberculosis of, 709 
Sweat-glands, 1007 
Swelling, cloudy, 78 
Sycosis, 1000 
Sylvius, aqueduct of, 884 



Symblepharon, 969 
Syncytioma malignum, 238 
of Fallopian tubes, 802 
Syncytium, 810 
Synophthalmia, 965 
Synovitis pannosa, 857 
Syphilis, bubo of, 336 

chancre of, 146, 336 

condyloma latum of, 146 

congenital, 338 

definition of, 334 

etiology of, 334 

gumma of, 146 

histology of, 145 

mucous patch of, 146 

of arteries, 511 
of brain, 901 

of bladder, 753 

of bones, 851 

of brain, 919 

of bronchi, 536 

of cervix, 782 

of choroid, 978 

of ciliary body, 977 

of conjunctiva, 969 

of cornea, 972 

of dura mater, 872, 929 

of esophagus, 612 

of external ear, 986 

of Fallopian tubes, 802 

of heart, 497 

of intestines, 647 

of iris, 975 

of joints, 861 

of kidneys, 741 

of larynx, 529 

of liver, 671 

of lungs, 578 

of lymphatic glands, 459 
vessels, 522 

of mammary glands, 831 

of middle ear, 988 

of mouth, 599 

of muscles, 869 

of nasal cavities, 525 

of nerves, 963 

of optic nerve, 982 

of pancreas, 689 

of pericardium, 502 

of pharynx, 607 

of pia-arachnoid, 879, 930 

of placenta, 812 

of pleura, 591 

of retina, 980 

of skin, 1003 

of spinal cord, 943 

of spleen, 450 

of suprarenal bodies, 710 

of testicles, 821 

of thymus gland, 712 

of thyroid, 705 

of trachea, 531 

of urethra, 770 

of vagina, 807 

of veins, 520 

of vulva, 809 



INDEX 



1041 



Syphilis, pathological anatomy of, 336 
physiology of, 338 
secondary lesions of, 336 
tertiary lesions of, 146, 337 

Syphilitic pneumonia, congenital, 563 

Syringomyelia, 935 



Tabardillo, 355 
Tabes dorsalis, 944 
Taenia echinococcus, 390 
saginata, 388 
solium, 386 

adult, in man, 387 
geographical distribution of, 387 
larval state, in man, 386 
Tape-worms, 384 

pathological physiology of, 385 
Teeth, 601 

■ anomalous development of, 601 

caries of, 601 

Hutchinson's, 339, 601 

inflammation of pulp of, 601 

odontomata of, 602 

tumors of, 602 
Telangiectasis, simple angiomatous, 991 
Tendon-sheaths, ganglion of, 862 

inflammation of, 862 
Tenosynovitis, 862 

gonorrheal, 769 
Terata, 239 
Teratoid tumors, 236 
Teratology, 235 
Teratoma, definition of, 235 

etiology of, 236 

of pia-arachnoid, 882 
Testicles, adenoma of, 822 

adenosarcoma of, 822 

anatomical considerations of, 816 

atrophy of, 817 

benign fungus of, 819 

calcification of, 817 

carcinoma of, 822 

caseation of, 817 

chondrocarcinoma of, 822 

chondroma of, 822 

congenital abnormalities of, 816 

cysts of, 823 

dermoid cysts of, 823 

echinococcus cysts of, 824 

embolism of spermatic artery of, 818 

fatty degeneration of, 817 

fibroma of, 822 

hyperemia of, 818 

hypertrophy of, 817 

hypoplasia of, 816 

lepra of, 822 

myxoma of, 822 

myxomatous degeneration of, 817 
osteoma of, 822 
papuliferous cystoma of, 823 
physiological considerations of, 816 
rhabdomyoma of, 822 
sarcoma of, 822 
syphilis of, 821 
syphilitic fungus of, 822 
66 



Testicles, tuberculosis of, 821 
Tetanolysin, 307 
Tetanospasmin, 307 
Tetanus, definition of, 306 

etiology of, 306 

pathological anatomy of, 307 
physiology of, 307 
Texas fever of cattle, 378 
Thalamencephalon, 883 
Thallophyta, 241 
Thelitis, 830 

Thoracic duct, diseases of, 523 
Thrombi, ball, 70 
Thrombin, 69 
Thrombo-angiitis, 506 
Thrombo-arteritis, 505 
Thrombophlebitis, 518 
Thrombosis, 67 

calcification after, 71 
canalization of, 72 
causes of, 67 
effects of, 70 
ferment, 68 
of bones, 841 
of brain, 908 
of cavities of heart, 471 
of coronary artery, 472 
of mesenteric arteries, 632 
of renal veins, 719 
of splenic vein, 445 
of veins of muscles, 863 
organization from, 72 
pathological anatomy of, 69 
subsequent changes in, 71 
Thrush, 347, 612 
Thymic asthma, 712 
Thymus gland, anatomy of. 711 

circulatory disturbances of, 712 
congenital abnormalities of, 711 
development of, 711 
inflammation of, 712 
syphilis of, 712 
tuberculosis of, 712 
tumors of, 712 
Thyroid disease, general results of, 706 
gland, abscess of, 700 
actinomycosis of, 705 
adenoma of, 705 

anatomical considerations of, 699 
circulatory disturbances in, 699 
congenital defects of, 699 
inflammation of, 700 
parasites of, 705 
sarcoma of, 705 
syphilis of, 705 
tuberculosis of, 705 
Thyroiditis, 700 
Tinea, 1004 
circinata, 1004 
sycosis, 1004 
tonsurans, 1004 
versicolor, 1004 
Tissue changes, progressive, 157 

destruction, excessive, 41 
Tongue, black, 598 
furring of, 595 



1042 



INDEX 



Tonsillitis, 604 
catarrhal, 604 
lacunar, 604 

pathological physiology of, 605 

phlegmonous, 605 
Tonsils, abscess of, 605 

hypertrophy of, 605 
Tophi, gouty, 46, 860 
Toxalbumins, 249 

from plants, poisoning from, 34 
Toxic enteritis, 633 
Toxin immunity, acquired, 260 

natural, 259 
Toxins of bacteria, 249 
Trachea, circulatory disturbances of, 531 

inflammation of, 531 

malformations of, acquired, 531 
congenital, 530 

syphilis of, 531 

tuberculosis of, 531 

tumors of, 531 
Trachoma, 362, 967 
Transitional leukocytes, 415 
Traumatic theory of carcinoma, 220 
Traumatism in etiology of disease, 24 
Trematodes, 380 
Treponema pallidum, 334 
Trichinella spiralis, 396 
Trichiniasis, 397 
Trichocephalus trichiurus, 401 
Trichomonas intestinalis, 367 

vaginalis, 368 
Trichorrhexis, 1008 
Trypanosoma, 369 

transmission of, 370 
Tubal abortion, 804 

pregnancy, 803 
Tube-casts, 733 
Tubercle, 995 

bacillus, 315. See also Bacillus tuber- 
culosis. 

foreign-body, 143 

structure and evolution of, 141 
Tuberculosis, 141 

bovine, 318 

bronchogenic, 567 

definition of, 313 

etiology of, 313 

fowl, 325 

hematogenic, 575 

latent, 322 

lymphogenic, 577 

miliary, 320 

of arteries, 511 

of bladder, 755 

of bones, 849 

of brain, 918 

of bronchi, 536 

of choroid, 978 
plexus, 923 

of ciliary body, 977 

of conjunctiva, 969 

of cornea, 972 

of dura mater, 872 

of esophagus, 612 

of external ear, 986 



Tuberculosis of Fallopian tubes, 801 
of heart, 497 
of intestines, 646 
of iris, 975 
of joints, 860 
of kidneys, 741, 750 
of larynx, 528 
of liver, 671 
of lungs, 566 

varieties of, 569 
of lymphatic glands, 456 

vessels, 522 
of mammary glands, 831 
of middle ear, 988 
of mouth, 599 
of muscles, 869 
of nasal cavities, 525 
of optic nerve, 982 
of ovaries, 792 
of pancreas, 689 
of penis, 815 
of pericardium, 502 
of peritoneum, 696 
of pharynx, 607 
of pia-arachnoid, 930 
of placenta, 812 
of pleura, 591 
of prostate, 825 
of retina, 980 
of skin, 1002 
of spinal cord, 943 
of spleen, 450 
of suprarenal bodies, 709 
of testicles, 821 
of thymus gland, 712 
of thyroid, 705 
of trachea, 531 
of urethra, 770 
of uterus, 782 
of vagina, 807 
of vas deferens, 821 
of veins, 520 
of vulva, 809 

pathological anatomy of, 319 
physiology of, 322 

pneumonic, acute, 569 
chronic, 570 

relation of human to animal, 318 

seats of, 321 
Tuberculous meningitis, 878 

pneumonia, 558 
Tubo-ovarian abscess, 792 

cysts, 802 _ 
Tumors, benign, 167 

classification of, 168 

Cohnheim's theory of, 160 

connective-tissue, 169 

definition of, 158 

epithelial, 212 

etiology of, 159 

Hansemann's theory of, 161 

infectious character ascribed to, 161 

malignant, 167 

metastasis of, 167 

mixed, 198, 236 

number of, 165 



INDEX 



1043 



Tumors of biliary tract, 683 
of bladder, 757 
of bones, 853 
of brain, 919 
of bronchi, 536 
of choroid, 978 

plexus, 923 
of ciliary bodv, 977 
of dura mater, 872, 929 
of esophagus, 612 
of external ear, 986 
of eye, 969 
of eyelids, 983 
of Fallopian tubes, 802 
of intestines, 648 
of iris, 976 
of joints, 862 
of kidneys, 741, 751 

secondary, 745 
of liver, 673 
of lungs, 580 
of lymphatic glands, 461 

vessels, 522 
of mammary glands, 831 
of middle ear, 989 
of mouth, 600 
of muscles, 869 
of nails, 1008 
of nasal cavities, 526 
of nerve tissues, 204 
of nerves, 963 
of optic nerve, 982 
of orbit, 983 

of ovaries, connective-tissue, 792 

cystic, 793 
of pancreas, 689 
of parotid gland, 609 
of penis, 815 
of pericardium, 502 
of peritoneum, 698 
of pharynx, 608 
of pia-arachnoid, 880, 931 
of pituitary body, 714 
of pleura, 592 
of prostate, 825 
of retina, 980 
of sebaceous glands, 1007 
of skin, 1005 
of spinal cord, 957 
of stomach, 622 
of suprarenal bodies, 711 
of teeth, 602 
of testicles, 822 
of thymus gland, 712 
of thyroid gland, 705 
of trachea, 531 
of urethra, 770 
of uterus, 784 
of vagina, 807 
of veins, 520 
of vulva, 809 

pathological physiology of, 166 
predisposing conditions, 163 
primary, 165 
Ribbert's theory of, 160 
secondary, 166 



Tumors, shape of, 165 
structure of, 163 
synonyms of, 158 
teratoid, 236 
Virchow's theory of, 160 
Tvmpanic membrane, 896 
Typhlitis, 636 
Typhoid fever, 642 

agglutination in, 292 
bacillus of, 289 
complications of, 645 
definition of, 289 
etiology of, 289 

Gruber-Durham phenomenon in, 
292 

pathological anatomy of, 292 

physiology of, 292 
Widal reaction in, 293 
ulceration of esophagus, 612 
Typhus fever, 355 
Tyroma, 879 
Tyrosin in urine, 766 
Tyrotoxicon, 36 



Ulcbb, 134 

gastric, 617 

of bronchi, 534 

of skin, 1002 

peptic, 617 

round, 617 
Ulcerative gastritis, 615 
Umbilical cord, velamentous insertion of, 

810 

Uncinaria americana, 399 

duodenalis, 397 
Unguis incarnatus, 100S 
Urates in urine, 765 
Uratic infiltration, 98 
Uremia in nephritis, 736 
Ureter, dilatation of, 748 

inflammation of, 750 

obstructions of, 748 
Ureteritis, 750 
Urethra, carcinoma of, 770 

congenital abnormalities of, 766 

cysts of, 770 

inflammation of, 767. See also Ure- 
thritis. 

injuries of, 770 

polypoid tumors of, 770 

sarcoma of, 770 

stricture of, 769 

syphilis of, 770 

tuberculosis of, 770 
Urethritis, 767 

anterior, 768 

gonorrheal, 770 

lesions associated with, 767 

pathological anatomy of, 767 

posterior, 768 

specific, 767 
Uric acid in urine, 764 
Urinary organs, diseases of, 717 
Urine, abnormal conditions of, 758 

bilirubin in, 766 



1044 



INDEX 



Urine, carbonates in, 766 

chemical changes in, 764 

cholesterin in, 766 

color of, 759 

cystin in, 766 

fat crystals in, 766 

hematoidin in, 766 

hemoglobin in, 766 

hippuric acid in, 765 

in nephritis, 733, 735 

indigo in, 766 

leucin in, 766 

methemoglobin in, 766 

oxalate of lime in, 764 

phosphates in, 764 

quantity of, 758 

reaction of, 759 

sediments in, 764 

specific gravity of, 759 

sulphates in, 766 

tyrosin in, 766 

urates in, 765 

uric acid in, 764 

xanthin in, 766 
Uriniferous tubules, concretions in, 740 
Urobilinuria, 760 
Urticaria, 994 

Uterus, adenofibroma of, 785 
adenoma of, 787 
adenomyoma of, 785 
anatomy of, 771 
anteflexion of, 772 
anteversion of, 772 
bicornis, 771 
carcinoma of, 788 
congenital abnormalities of, 771 
cysts of, 790 
development of, 771 
dilatation of, 775 
duplexus, 772 
erosions of, 779 
fatty degeneration of, 783 
fibroids of, 784 
hemorrhage from, 776 
hyperemia of, 775 

hyperplasia of mucous membrane of, 
783 

hypertrophy of, 783 

infantilis, 771 

infectious diseases of, 780 

inversion of, 773 

lateral displacements of, 773 

leiomyoma of, 784 

myofibroma of, 784 

parasites of, 790 

polypi, 783 

prolapse of, 773 

puerperal atrophy of, 783 

retroflexion of, 773 

retroversion of, 773 

rupture of, 775 

sarcoma of, 785 

senile atrophy of, 783 

septus, 771 

stenosis of, 775 

tuberculosis of, 782 



Uterus unicornis, 772 

upward dislocation of, 773 
Uveal tract, hyperemia of, 975 



Vaccinia, 354 
Vacuolization, 894 
Vagina, carcinoma of, 807 

cysts of, 807 

fibroma of, 807 

hemorrhage into walls of, 806 

hyperemia of, 806 

myofibroma of, 807 

papilloma of, 807 

prolapse of walls of, 805 

sarcoma of, 807 

stenosis of, 805 

syphilis of, 807 

tuberculosis of, 807 
Vaginal cystocele, 805 

rectocele, 805 
Vaginitis, aphthous, 806 

chronic catarrhal, 806 

emphysematous, 806 

erysipeloid, 806 

exfoliative, 806 

pseudomembranous, 806 

senile, 806 

testis, 818, 819 
hemorrhagic, 820 
purulent, 820 
serous, 819 
Varicella, 355, 996 
Varicocele, 820 

Varicose veins of spinal cord, 937 
Varicosity, 519 
Variola, 354, 966 

Vas deferens, inflammation of, 820 

tuberculosis of, 821 
Vasomotor disturbances, 57 
Veins, 517 

anatomical considerations of, 517 

calcification of, 518 

circulatory disturbances of, 517 

dilatation of, 519 

fatty degeneration of, 518 

syphilis of, 520 

tuberculosis of, 520 

tumors of, 520 
Venereal wart, 212 
Ventricles, ependymitis of, 923 
Ventricular septum, defects of, 469 
Vermes, 380 
Verruca, 992 
Vesicles, 995 

Vibrio cholera; asiaticae, 330 

organisms resembling, 333 
Vincent's angina, 340, 607 
Virchow's theory of inflammation, 118 

of tumors, 160 
Virus of rabies, 356 
Viruses, filterable, 351 
Vitiligo, 993 
Vitreous humor, 965 

chemical changes in, 974 

hemorrhage into, 974 



INDEX 



1045 



Vitreous humor, inflammation of, 974 
Volvulus of intestines, 629 
Vulva, 807 

abscess of, 808 

adenoma of, 809 

carcinoma of, 809 

caruncle of, 809 

chancroids of, 809 

cysts of, 809 

diphtheria of, 809 

edema of, 808 

elephantiasis of, 809 

fibroma of, 809 

fibromyxoma of, 809 

gangrene of, 809 

hematoma of, 808 

hyperemia of, 808 

inflammation of, acute catarrhal, 808 

chronic, 808 

phlegmonous, 808 
lipoma of, 809 
myofibroma of, 809 
papillomatous tumors of, 809 
sarcoma of, 809 
syphilis of, 809 
tuberculosis of, 809 
wounds of, 808 



Water transmission of disease, 409 

Wen, 991, 1007 

White corpuscles, 414 

Whooping-cough, Bordet-Gengou bacil- 
lus of, 299 

Widal reaction in typhoid fever, 292 

Wine stain, 991 

Wounds of cornea, 972 
repair of, 137 
tissue changes from, 24 



Xanthin in urine, 766 
Xanthoma, definition of, 175 

nature of, 176 

of skin, 1005. 

structure of, 175 
Xerosis, 969 

X-ray in etiology of disease, 29 



Yaws, 341 

Yellow atrophy of liver, acute, 659 
fever, definition of, 351 
etiology of, 351 
pathological anatomy of, 352 

physiology of, 352 
role of mosquitoes in, 351 



Warts, 992 
venereal, 212 



ZtJCKERGTJSSLEBER, 670, 696 



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THIRD EDITION— WITH 212 ILLUSTRATIONS, 32 IN COLORS 

This edition represents all the advances recently made in the science of em- 
bryology. Many portions have been entirely rewritten, and a great deal of new 
and important matter added. A number of new illustrations have also been intro- 
duced and these will prove very valuable. Heisler' s Embryology has become 
a standard work. 

G. Carl Huber. M. D.. 

Professor of Embryology at the Wis tar Institute, University of Pennsylania. 
" I find this edition of 'A Text-Book of Embryology,' by Dr. Heisler, an improvement 
on the former one. The figures added increase greatly the value of the work. I am again 
recommending it to our students." 

Bohm, Davidoff, and 
Huber's Histology 

A Text-Book of Human Histology. Including Microscopic Tech- 
nic. By Dr. A. A. Bohm and Dr. M. Von Davidoff, of Munich, and 
G. Carl Huber, M. D., Professor of Embryology at the Wistar Insti- 
tute, University of Pennsylvania. Handsome octavo of 528 pages, with 
361 beautiful original illustrations. Flexible cloth, $3.50 net. 

SECOND EDITION. ENLARGED 

The work of Drs. Bohm and Davidoff is well known in the German edition, 
and has been considered one of the most practically useful books on the subject 
of Human Histology. This second edition has been in great part rewritten and 
very much enlarged by Dr. Huber, who has also added over one hundred original 
illustrations. Dr. Huber's extensive additions have rendered the work the most 
complete students' text-book on Histology in existence. 

Boston Medical and Surgical Journal 

" Is unquestionably a text-book of the first rank, having been carefully written by thorough 
masters of the subject, and in certain directions it is much superior to any other histological 
manual." 



IO 



SAUNDERS' BOOKS ON 



Wells' Chemical Pathology 



Chemical Pathology. — Being a Discussion of General Pathology 
from the Standpoint of the Chemical Processes Involved. By H. 
Gideon Wells, Ph. D., M. D., Assistant Professor of Pathology in the 
University of Chicago. Octavo of 61 6 pages. Cloth, $3.25 net. 

NEW (2d) EDITION 

Dr. Wells' work is written for the physician, for those engaged in research in 
pathology and physiologic chemistry, and for the medical student. In the intro- 
ductory chapter are discussed the chemistry and physics of the animal cell, giving 
the essential facts of ionization, diffusion, osmotic pressure, etc., and the relation 
of these facts to cellular activities. Special chapters are devoted to Diabetes and 
to Uric-acid Metabolism and Gout. 

Wm. H. Welch, M. D. 

Professor of Pathology, Johns Hopkins University. 

" The work fills a real need in the English literature of a very important subject, and I 
shall be glad to recommend it to my students." 

Lusk's 
Elements of Nutrition 

Elements of the Science of Nutrition. By Graham Lusk, Ph. D., 
Professor of Physiology at Cornell Medical School. Octavo volume 
of 302 pages. Cloth, $3.00 net. 

THE NEW (2d) EDITION— TRANSLATED INTO GERMAN 

Prof. Lusk presents the scientific foundations upon which rests our knowledge 
of nutrition and metabolism, both in health and in disease. There are special 
chapters on the metabolism of diabetes and fever, and on purin metabolism. 
The work will also prove valuable to students of animal dietetics at agricultural 
stations. 

Lewellys F. Barker, M. D. 

Professor of the Principles and Practice of Medicine, Johns Hopkins University. 
" I shall recommend it highly to my students. It is a comfort to have such a discussion 
of the subject in English." 



HISTOLOGY. 



ii 



Daugherty's 
Economic Zoology 

Economic Zoology. By L. S. Daugherty, M. S., Ph. D., Professor 
of Zoology, State Normal School, Kirksville, Mo., and M. C. Daugh- 
erty, author with Jackson of " Agriculture Through the Laboratory 
and School Garden." Part I: Field and Laboratory Guide. l2mo of 
237 pages, interleaved. Cloth, $1.25 net. Part II: Principles. i2mo 
of 406 pages, illustrated. Cloth, $2.00 net. 

ILLUSTRATED 



There is no other book just like this. Not only does it give the salient facts 
of structural zoology and the development of the various branches of animals, but 
also the natural history — the life and habits — thus showing the interrelations of 
structure, habit, and environment. In a word, it gives the principles of zoology 
and their actual application. The economic phase is emphasized. 
Part I — the Field and Laboratory Guide — is designed for practical instruction in 
the field and laboratory. To enhance its value for this purpose blank pages are 
inserted for notes. 

DrewV 
Invertebrate Zoology 

A Laboratory Manual of Invertebrate Zoology. By Gilman A. 
Drew, Ph.D., Assistant Director at Marine Biological Laboratory, Woods 
Hole, Mass. With the aid of Former and Present Members of the Zoological 
Staff of Instructors. i2mo of 213 pages. Cloth, $1.25 net. 

NEW (2d) EDITION 

The subject is presented in a logical way, and the type method of study has 
been followed, as this method has been the prevailing one for many years. 

Prof. Allison A. Smyth, Jr., Virginia Polytechnic Institute 

" I think it is the best laboratory manual of zoology I have yet seen. The large number 
of forms dealt with makes the work applicable to almost any locality." 



12 



SAUNDERS BOOKS ON 



Norris' Cardiac Pathology 

Studies in Cardiac Pathology. By George W. Norris, M.D., 
Associate in Medicine at the University of Pennsylvania. Large octavo 
of 235 pages, with 85 superb illustrations. Cloth, $5.00 net. 

SUPERB ILLUSTRATIONS 

The illustrations are superb. Each illustration is accompanied by a detailed 
description; besides, there is ample letter press supplementing the pictures. 

Boston Medical and Surgical Journal 

" The illustrations are arranged in such a way as to illustrate all the common and many of 
the rare cardiac lesions, and the accompanying descriptive text constitutes a fairly continuous 
didactic treatise." 



McConnell's Pathology 

A Manual of Pathology. By Guthrie McConnell, M. D., As- 
sistant Surgeon, Medical Reserve Corps, U. S. Navy. i2mo of 523 
pages, with 170 illustrations. Flexible leather, $2.50 net. 

NEW (2d) EDITION 

Dr. McConnell has discussed his subject with a clearness and precision of 
style that make the work of great assistance to both student and practitioner. 
The illustrations have been introduced for their practical value. 

New York State Journal of Medicine 

" The book treats the subject of pathology with a thoroughness lacking in many works of 
greater pretension. The illustrations — many of them original — are profuse and of exceptional 
excellence." 



McConnell's Pathology and Bacteriology Fo It!tt! 

Pathology and Bacteriology for Dental Students. By Guthrie 
McConnell, M. D., Assistant Surgeon, Medical Reserve Corps, U. S. N. 
i2mo of 309 pages, illustrated. Cloth, $2.25 net. 

JUST ISSUED 

This work is written expressly for dentists and dental students, emphasizing 
throughout the application of pathology and bacteriology in dental study and prac- 
tice. There are chapters on disorders of metabolism and circulation; retro- 
gressive processes, cell division inflammation and regeneration, granulomas, pro- 
gressive processes, tumors, special mouth pathology, sterilization and disinfection, 
bacteriologic methods, specific micro-organisms, infection and immunity, and 
laboratory technic. 



HISTOLOGY. 



13 



Dtirck and Hektoen's 

Special Pathologic Histology 

Atlas and Epitome of Special Pathologic Histology. By Dr. H. 

Durck, of Munich. Edited, with additions, by Ludvig Hektoen, M. D., 
Professor of Pathology, Rush Medical College, Chicago. In two parts. 
Part I. — Circulatory, Respiratory, and Gastro-intestinal Tracts. 120 
colored figures on 62 plates, and 158 pages of text. Part II. — Liver, 
Urinary and Sexual Organs, Nervous System, Skin, Muscles, and 
Bones. 123 colored figures on 60 plates, and 192 pages of text. Per 
part : Cloth, $3.00 net. In Saunders' Hand-Atlas Series. 

The great value of these plates is that they represent in the exact colors the effect 
of the stains, which is of such great importance for the differentiation of tissue. 
The text portion of the book is admirable, and, while brief, it is entirely satisfac- 
tory in that the leading facts are stated, and so stated that the reader feels he has 
grasped the subject extensively. 

William H. Welch, M. D., 

Professor of Pathology, Johns Hopkins University, Baltimore. 

" I consider Diirck's 'Atlas of Special Pathologic Histology,' edited by Hektoen, a very 
useful book for students and others. The plates are admirable." 

Sobotta and Huber's 
Human Histology 

Atlas and Epitome of Human Histology. By Privatdocent Dr. 
J. Sobotta, of Wiirzburg. Edited, with additions, by G. Carl Huber, 
M. D., Professor of Histology and Embryology in the University of 
Michigan, Ann Arbor. With 214 colored figures on 80 plates, 68 
text-illustrations, and 248 pages of text. Cloth, $4.50 net. In 
Saunders" Hand- Atlas Series. 

INCLUDING MICROSCOPIC ANATOMY 

The work combines an abundance of well-chosen and most accurate illustra- 
tions, with a concise text, and in such a manner as to make it both atlas and text- 
book. The great majority of the illustrations were made from sections prepared 
from human tissues, and always from fresh and in every respect normal specimens. 
The colored lithographic plates have been produced with the aid of over thirty colors. 

Boston Medical and Surgical Journal 

" In color and proportion they are characterized by gratifying accuracy and lithographic 
beauty." 



SAUNDERS" BOOKS ON 



Bosanquet on Spirochaetes 

Spirochetes : A Review of Recent Work, with Some Original Ob- 
servations. By W. Cecil Bosanquet, M.D., Fellow of the Royal Col- 
lege of Physicians, London. Octavo of 152 pages, illustrated. $2.50 net. 

ILLUSTRATED 

This is a complete and authoritative monograph on the spirochaetes, giving 
morphology, pathogenesis, classification, staining, etc. Pseudospirochaetes are 
also considered, and the entire text well illustrated. The high standing of Dr. 
Bosanquet in this field of study makes this new work particularly valuable. 

Levy and Klemperer's 
Clinical Bacteriology 

The Elements of Clinical Bacteriology. By Drs. Ernst Levy and 
Felix Klemperer, of the University of Strasburg. Translated and 
edited by Augustus A. Eshner, M. D., Professor of Clinical Medicine, 
Philadelphia Polyclinic. Octavo volume of 440 pages, fully illustrated. 
Cloth, $2.50 net. 

S. Solis-Cohen, M. D.. 

Professor of Clinical Medicine, Jefferson Medical College, Philadelphia. 

" I consider it an excellent book. I have recommended it in speaking to my students." 

Lehmann, Neumann, and 
Weaver's Bacteriology 

Atlas and Epitome of Bacteriology : including a Text-Book of 
Special Bacteriologic Diagnosis. By Prof. Dr. K. B. Lehmann 
and Dr. R. O. Neumann, of Wurzburg. From the Second Revised and 
Enlarged German Edition. Edited, with additions, by G. H. Weaver, 
M. D., Assistant Professor of Pathology and Bacteriology, Rush Medical 
College, Chicago. In two parts. Part I. — 632 colored figures on 69 
lithographic plates. Part II. — 5 1 1 pages of text, illustrated. Per part: 
Cloth, $2.50 net. In Saunders' Hand-Atlas Series. 



PATHOLOGY, BACTERIOLOGY, AND PATHOLOGY 



1 5 



Durck and Hektoen's General Pathologic Histology 

Atlas and Epitome of General Pathologic Histology. By Pr. 
Dr. H. Durck, of Munich. Edited, with additions, by Ludvig Hek- 
toen, M. D., Professor of Pathology in Rush Medical College, Chicago. 
172 colored figures on 77 lithographic plates, 36 text-cuts, many 
in colors, and 353 pages. Cloth, $5.00 net. In Saunders' Hand- Atlas 
Series. 

American Text-Book of Physiology second Edition 

American Text-Book of Physiology. In two volumes. Edited by 
William H. Howell, Ph. D., M.D., Professor of Physiology in the Johns 
Hopkins University, Baltimore, Md. Two royal octavos of about 600 
pages each, illustrated. Per volume: Cloth, $3.00 net; Half Morocco, 
$4.25 net. 

" The work will stand as a work of reference on physiology. To him who desires to know 
the status of modern physiology, who expects to obtain suggestions as to further physio- 
logic inquiry, we know of none in English which so eminently meets such a demand." — 
The Medical News. 

Warren's Pathology and Therapeutics second Edition 

Surgical Pathology and Therapeutics. By John Collins Warren, 
M. D., LL.D., F. R. C. S. (Hon.), Professor of Surgery, Harvard Med- 
ical School. Octavo, 873 pages, 136 relief and lithographic illustrations, 
33 in colors. With an Appendix on Scientific Aids to Surgical Diagnosis 
and a series of articles on Regional Bacteriology. Cloth, $5.00 net; 
Half Morocco, $6.50 net. 

Gorham's Bacteriology 

A Laboratory Course in Bacteriology. For the Use of Medical, 
Agricultural, and Industrial Students. By Frederic P. Gorham, A. M., 
Associate Professor of Biology in Brown University, Providence, R. I., 
etc. i2mo of 192 pages, with 97 illustrations. Cloth, $1.25 net. 

" One of the best students' laboratory guides to the study of bacteriology on the mar- 
ket. . . . The technic is thoroughly modern and amply sufficient for all practical pur- 
poses." — American Journal of the Medical Sciences. 

Raymond's Physiology New (3d) Edition 

Human Physiology. By Joseph H. Raymond, A. M., M. D., Pro- 
fessor of Physiology and Hygiene, Long Island College Hospital, New 
York. Octavo of 685 pages, with 444 illustrations. Cloth, $3.50 net. 

" The book is well gotten up and well printed, and may be regarded as a trustworthy 
guide for the student and a useful work of reference for the general practitioner. The 
illustrations are numerous and are well executed." — The Lancet, London. 



16 BACTERIOLOGY, PHYSIOLOGY, AND HISTOLOGY. 

Ball's Bacteriology Seventh Edition, Revised 

Essentials of Bacteriology : being a concise and systematic intro- 
duction to the Study of Micro-organisms. By M. V. Ball, M. D., Late 
Bacteriologist to St. Agnes' Hospital, Philadelphia. 12 mo of 289 pages, 
with 135 illustrations, some in colors. Cloth, $1.00 net. In Saunders* 
Question- Compend Series. 

" The technic with regard to media, staining, mounting, and the like is culled from the 
latest authoritative works." — The Afedical Times, New York. 

Blldgett'S Physiology New (3d) Edition 

Essentials of Physiology. Prepared especially for Students of Medi- 
cine, and arranged with questions following each chapter. By Sidney 
P. Budgett, M. D., formerly Professor of Physiology, Washington Uni- 
versity, St. Louis. Revised by Havan Emerson, M. D., Demonstrator 
of Physiology, Columbia University. i2mo volume of 250 pages, illus- 
trated. Cloth, $ 1 . 00 net. Saunders' Question- Compend Series. 

"He has an excellent conception of his subject. . . It is one of the most satisfactory 
books of this class" — University of Pennsylvania Medical Bulletin. 

Leroy's Histology New (4th) Edition 

Essentials of Histology. By Louis Leroy, M. D., Professor of 
Histology and Pathology, Vanderbilt University, Nashville, Tennessee. 
i2mo, 263 pages, with 92 original illustrations. Cloth, $1.00 net. In 

Saunders' Question- Compend Series. 

" The work in its present form stands as a model of what a student's aid should be ; and 
we unhesitatingly say that the practitioner as well would find a glance through the book 
of lasting benefit." — -The Medical World, Philadelphia. 

Barton and Wells' Medical Thesaurus 

A Thesaurus of Medical Words and Phrases. By Wilfred M. 
Barton, M. D., Assistant Professor of Materia Medica and Therapeutics, 
and Walter A. Wells, M.D., Demonstrator of Laryngology, Georgetown 
University, Washington, D. C. i2mo, 534 pages. Flexible leather, 
$2.50 net; thumb indexed, $3.00 net. 

American Pocket Medical Dictionary New (9t h) J Edit?o U n 

American Pocket Medical Dictionary. Edited by W. A. New- 
man Dorland, M. D., Editor "American Illustrated Medical Dic- 
tionary." Containing the pronunciation and definition of the principal 
words used in medicine and kindred sciences, with 75 extensive tables. 
693 pages. Flexible leather, with gold edges, $1.00 net; with patent 
thumb index, $1.25 net. 

" I can recommend it to our students without reserve." — J. H. HOLLAND, M. D., of 

the Jefferson Medical College, Philadelphia. 



